Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2015 (2015), Article ID 135342, 15 pages
http://dx.doi.org/10.1155/2015/135342
Review Article

Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo

1Neuroscience Institute (CNR), Via Vanvitelli 32, 20129 Milano, Italy
2Department of BIOMETRA, University of Milano, Via Vanvitelli 32, 20129 Milano, Italy
3Laboratory of Neuroscience “R. Levi-Montalcini”, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
4SYSBIO Centre of Systems Biology, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
5NeuroMI Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milano, Italy

Received 27 March 2015; Accepted 25 June 2015

Academic Editor: Stuart C. Mangel

Copyright © 2015 Stefano Morara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. N. Serhan, N. Chiang, J. Dalli, and B. D. Levy, “Lipid mediators in the resolution of inflammation,” Cold Spring Harbor Perspectives in Biology, vol. 7, no. 2, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Ortega-Gómez, M. Perretti, and O. Soehnlein, “Resolution of inflammation: an integrated view,” EMBO Molecular Medicine, vol. 5, no. 5, pp. 661–674, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. S. S. Pullamsetti, R. Savai, W. Janssen et al., “Inflammation, immunological reaction and role of infection in pulmonary hypertension,” Clinical Microbiology and Infection, vol. 17, no. 1, pp. 7–14, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. J. V. Bonventre and L. Yang, “Cellular pathophysiology of ischemic acute kidney injury,” Journal of Clinical Investigation, vol. 121, no. 11, pp. 4210–4221, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Weber and H. Noels, “Atherosclerosis: current pathogenesis and therapeutic options,” Nature Medicine, vol. 17, no. 11, pp. 1410–1422, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. P. A. B. Wark, V. Murphy, and J. Mattes, “The interaction between mother and fetus and the development of allergic asthma,” Expert Review of Respiratory Medicine, vol. 8, no. 1, pp. 57–66, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. X. Zhang and J. Köhl, “A complex role for complement in allergic asthma,” Expert Review of Clinical Immunology, vol. 6, no. 2, pp. 269–277, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. I. Schmudde, Y. Laumonnier, and J. Köhl, “Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma,” Seminars in Immunology, vol. 25, no. 1, pp. 2–11, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. V. O. Millien, W. Lu, G. Mak et al., “Airway fibrinogenolysis and the initiation of allergic inflammation,” Annals of the American Thoracic Society, vol. 11, supplement 5, pp. S277–S283, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. J. L. Barlow and A. N. J. McKenzie, “Type-2 innate lymphoid cells in human allergic disease,” Current Opinion in Allergy and Clinical Immunology, vol. 14, no. 5, pp. 397–403, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. P. Shivshankar, G. V. Halade, C. Calhoun et al., “Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction,” Journal of Molecular and Cellular Cardiology, vol. 76, pp. 84–93, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. K. J. Moore, F. J. Sheedy, and E. A. Fisher, “Macrophages in atherosclerosis: a dynamic balance,” Nature Reviews Immunology, vol. 13, no. 10, pp. 709–721, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. I. Galea, I. Bechmann, and V. H. Perry, “What is immune privilege (not)?” Trends in Immunology, vol. 28, no. 1, pp. 12–18, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. R. M. Ransohoff and B. Engelhardt, “The anatomical and cellular basis of immune surveillance in the central nervous system,” Nature Reviews Immunology, vol. 12, no. 9, pp. 623–635, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Helmut, U.-K. Hanisch, M. Noda, and A. Verkhratsky, “Physiology of microglia,” Physiological Reviews, vol. 91, no. 2, pp. 461–553, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Nimmerjahn, F. Kirchhoff, and F. Helmchen, “Neuroscience: resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo,” Science, vol. 308, no. 5726, pp. 1314–1318, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. D. Davalos, J. Grutzendler, G. Yang et al., “ATP mediates rapid microglial response to local brain injury in vivo,” Nature Neuroscience, vol. 8, no. 6, pp. 752–758, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. H. Wake, A. J. Moorhouse, S. Jinno, S. Kohsaka, and J. Nabekura, “Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals,” The Journal of Neuroscience, vol. 29, no. 13, pp. 3974–3980, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. R. C. Paolicelli, G. Bolasco, F. Pagani et al., “Synaptic pruning by microglia is necessary for normal brain development,” Science, vol. 333, no. 6048, pp. 1456–1458, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Zhan, R. C. Paolicelli, F. Sforazzini et al., “Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior,” Nature Neuroscience, vol. 17, no. 3, pp. 400–406, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. D. P. Schafer, E. K. Lehrman, A. G. Kautzman et al., “Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner,” Neuron, vol. 74, no. 4, pp. 691–705, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Li, X.-F. Du, C.-S. Liu, Z.-L. Wen, and J.-L. Du, “Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo,” Developmental Cell, vol. 23, no. 6, pp. 1189–1202, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Cunningham, “Microglia and neurodegeneration: the role of systemic inflammation,” Glia, vol. 61, no. 1, pp. 71–90, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. V. H. Perry and J. Teeling, “Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration,” Seminars in Immunopathology, vol. 35, no. 5, pp. 601–612, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. D. M. Norden, M. M. Muccigrosso, and J. P. Godbout, “Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease,” Neuropharmacology, vol. 96, part A, pp. 29–41, 2015. View at Publisher · View at Google Scholar
  26. V. H. Perry and C. Holmes, “Microglial priming in neurodegenerative disease,” Nature Reviews Neurology, vol. 10, no. 4, pp. 217–224, 2014. View at Publisher · View at Google Scholar · View at Scopus
  27. J. C. Delpech, C. Madore, A. Nadjar, C. Joffre, E. S. Wohleb, and S. Layé, “Microglia in neuronal plasticity: influence of stress,” Neuropharmacology, vol. 96, pp. 19–28, 2015. View at Publisher · View at Google Scholar
  28. C. Cunningham, D. C. Wilcockson, S. Campion, K. Lunnon, and V. H. Perry, “Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration,” The Journal of Neuroscience, vol. 25, no. 40, pp. 9275–9284, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Field, S. Campion, C. Warren, C. Murray, and C. Cunningham, “Systemic challenge with the TLR3 agonist poly I: C induces amplified IFNα/β and IL-1β responses in the diseased brain and exacerbates chronic neurodegeneration,” Brain, Behavior, and Immunity, vol. 24, no. 6, pp. 996–1007, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. M. C. P. Godoy, R. Tarelli, C. C. Ferrari, M. I. Sarchi, and F. J. Pitossi, “Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease,” Brain, vol. 131, no. 7, pp. 1880–1894, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. G. Purisai, A. L. McCormack, S. Cumine, J. Li, M. Z. Isla, and D. A. Di Monte, “Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration,” Neurobiology of Disease, vol. 25, no. 2, pp. 392–400, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. D. M. Norden and J. P. Godbout, “Review: microglia of the aged brain: primed to be activated and resistant to regulation,” Neuropathology and Applied Neurobiology, vol. 39, no. 1, pp. 19–34, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Kumar, B. A. Stoica, B. Sabirzhanov, M. P. Burns, A. I. Faden, and D. J. Loane, “Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states,” Neurobiology of Aging, vol. 34, no. 5, pp. 1397–1411, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Palin, C. Cunningham, P. Forse, V. H. Perry, and N. Platt, “Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration,” Neurobiology of Disease, vol. 30, no. 1, pp. 19–29, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. M. D. Weber, M. G. Frank, K. J. Tracey, L. R. Watkins, and S. F. Maier, “Stress induces the danger-associated molecular pattern HMGB-1 in the hippocampus of male sprague dawley rats: a priming stimulus of microglia and the NLRP3 inflammasome,” Journal of Neuroscience, vol. 35, no. 1, pp. 316–324, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. A. M. Fenn, J. C. Gensel, Y. Huang, P. G. Popovich, J. Lifshitz, and J. P. Godbout, “Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia,” Biological Psychiatry, vol. 76, no. 7, pp. 575–584, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. L. R. Frick, K. Williams, and C. Pittenger, “Microglial dysregulation in psychiatric disease,” Clinical and Developmental Immunology, vol. 2013, Article ID 608654, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Prinz and J. Priller, “Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease,” Nature Reviews Neuroscience, vol. 15, no. 5, pp. 300–312, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Akiyama and P. L. McGeer, “Microglial response to 6-hydroxydopamine-induced substantia nigra lesions,” Brain Research, vol. 489, no. 2, pp. 247–253, 1989. View at Publisher · View at Google Scholar · View at Scopus
  40. J. W. Francis, J. Von Visger, G. J. Markelonis, and T. H. Oh, “Neuroglial responses to the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse striatum,” Neurotoxicology and Teratology, vol. 17, no. 1, pp. 7–12, 1995. View at Publisher · View at Google Scholar · View at Scopus
  41. L. Facci, M. Barbierato, C. Marinelli, C. Argentini, S. D. Skaper, and P. Giusti, “Toll-like receptors 2, -3 and -4 prime microglia but not astrocytes across central nervous system regions for ATP-dependent interleukin-1β release,” Scientific Reports, vol. 4, article 6824, 2014. View at Publisher · View at Google Scholar
  42. M. D. Weber, M. G. Frank, J. L. Sobesky, L. R. Watkins, and S. F. Maier, “Blocking toll-like receptor 2 and 4 signaling during a stressor prevents stress-induced priming of neuroinflammatory responses to a subsequent immune challenge,” Brain, Behavior, and Immunity, vol. 32, pp. 112–121, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Schilling and C. Eder, “Amyloid-β-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia,” Journal of Cellular Physiology, vol. 226, no. 12, pp. 3295–3302, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Qin and F. T. Crews, “Chronic ethanol increases systemic TLR3 agonist-induced neuroinflammation and neurodegeneration,” Journal of Neuroinflammation, vol. 9, article 130, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Roodveldt, A. Labrador-Garrido, E. Gonzalez-Rey et al., “Preconditioning of microglia by α-synuclein strongly affects the response induced by toll-like receptor (TLR) stimulation,” PLoS ONE, vol. 8, no. 11, Article ID e79160, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. J. D. Johnson, Z. R. Zimomra, and L. T. Stewart, “Beta-adrenergic receptor activation primes microglia cytokine production,” Journal of Neuroimmunology, vol. 254, no. 1-2, pp. 161–164, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Parajuli, Y. Sonobe, J. Kawanokuchi et al., “GM-CSF increases LPS-induced production of proinflammatory mediators via upregulation of TLR4 and CD14 in murine microglia,” Journal of Neuroinflammation, vol. 9, article 268, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. H.-M. Lee, J. Kang, S. J. Lee, and E.-K. Jo, “Microglial activation of the NLRP3 inflammasome by the priming signals derived from macrophages infected with mycobacteria,” Glia, vol. 61, no. 3, pp. 441–452, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. D. D. A. Raj, D. Jaarsma, I. R. Holtman et al., “Priming of microglia in a DNA-repair deficient model of accelerated aging,” Neurobiology of Aging, vol. 35, no. 9, pp. 2147–2160, 2014. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Pawate, Q. Shen, F. Fan, and N. R. Bhat, “Redox regulation of glial inflammatory response to lipopolysaccharide and interferon gamma,” Journal of Neuroscience Research, vol. 77, no. 4, pp. 540–551, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. D. Kim, B. You, E.-K. Jo, S.-K. Han, M. I. Simon, and S. J. Lee, “NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 33, pp. 14851–14856, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. M. L. Block, L. Zecca, and J.-S. Hong, “Microglia-mediated neurotoxicity: uncovering the molecular mechanisms,” Nature Reviews Neuroscience, vol. 8, no. 1, pp. 57–69, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. M. T. Fischer, R. Sharma, J. L. Lim et al., “NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury,” Brain, vol. 135, no. 3, pp. 886–899, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. E. A. Bordt and B. M. Polster, “NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair?” Free Radical Biology and Medicine, vol. 76, pp. 34–46, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. R. P. Brandes, N. Weissmann, and K. Schröder, “Nox family NADPH oxidases: molecular mechanisms of activation,” Free Radical Biology and Medicine, vol. 76, pp. 208–226, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. A. I. Rojo, G. McBean, M. Cindric et al., “Redox control of microglial function: molecular mechanisms and functional significance,” Antioxidants & Redox Signaling, vol. 21, no. 12, pp. 1766–1801, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. C. S. Jack, N. Arbour, J. Manusow et al., “TLR signaling tailors innate immune responses in human microglia and astrocytes,” Journal of Immunology, vol. 175, no. 7, pp. 4320–4330, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. J. K. Olson and S. D. Miller, “Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs,” Journal of Immunology, vol. 173, no. 6, pp. 3916–3924, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Husemann, J. D. Loike, T. Kodama, and S. C. Silverstein, “Scavenger receptor class B type I (SR-BI) mediates adhesion of neonatal murine microglia to fibrillar β-amyloid,” Journal of Neuroimmunology, vol. 114, no. 1-2, pp. 142–150, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. I. S. Coraci, J. Husemann, J. W. Berman et al., “CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to β-amyloid fibrils,” American Journal of Pathology, vol. 160, no. 1, pp. 101–112, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. O. Arancio, H. P. Zhang, X. Chen et al., “RAGE potentiates Aβ-induced perturbation of neuronal function in transgenic mice,” The EMBO Journal, vol. 23, no. 20, pp. 4096–4105, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Akiyama and P. L. McGeer, “Brain microglia constitutively express β-2 integrins,” Journal of Neuroimmunology, vol. 30, no. 1, pp. 81–93, 1990. View at Publisher · View at Google Scholar · View at Scopus
  63. Z. Pei, H. Pang, L. Qian et al., “MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity,” Glia, vol. 55, no. 13, pp. 1362–1373, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. A. M. Colangelo, L. Alberghina, and M. Papa, “Astrogliosis as a therapeutic target for neurodegenerative diseases,” Neuroscience Letters, vol. 565, pp. 59–64, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. C. Cavaliere, G. Cirillo, M. R. Rosaria Bianco et al., “Gliosis alters expression and uptake of spinal glial amino acid transporters in a mouse neuropathic pain model,” Neuron Glia Biology, vol. 3, no. 2, pp. 141–153, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Takaki, K. Fujimori, M. Miura, T. Suzuki, Y. Sekino, and K. Sato, “L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the ‘collusion’ hypothesis for increased extracellular L-glutamate concentration in neuroinflammation,” Journal of Neuroinflammation, vol. 9, article 275, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. A. M. Colangelo, G. Cirillo, M. L. Lavitrano, L. Alberghina, and M. Papa, “Targeting reactive astrogliosis by novel biotechnological strategies,” Biotechnology Advances, vol. 30, no. 1, pp. 261–271, 2012. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Persson and L. Rönnbäck, “Microglial self-defence mediated through GLT-1 and glutathione,” Amino Acids, vol. 42, no. 1, pp. 207–219, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Chen, E. Jacobs, M. A. Schwarzschild et al., “Nonsteroidal anti-inflammatory drug use and the risk of Parkinson's disease,” Annals of Neurology, vol. 59, pp. 988–989, 2005. View at Google Scholar
  70. W. J. Lukiw, “Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling,” Neurochemical Research, vol. 29, no. 6, pp. 1287–1297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. W. J. Streit, N. W. Sammons, A. J. Kuhns, and D. L. Sparks, “Dystrophic microglia in the aging human brain,” Glia, vol. 45, no. 2, pp. 208–212, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. M. P. Mattson and T. Magnus, “Ageing and neuronal vulnerability,” Nature Reviews Neuroscience, vol. 7, no. 4, pp. 278–294, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. R. Banerjee, “Redox outside the box: linking extracellular redox remodeling with intracellular redox metabolism,” The Journal of Biological Chemistry, vol. 287, no. 7, pp. 4397–4402, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Bournival, P. Quessy, and M.-G. Martinoli, “Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons,” Cellular and Molecular Neurobiology, vol. 29, no. 8, pp. 1169–1180, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Morini, L. Roccatagliata, R. Dell'Eva et al., “α-Lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis,” Journal of Neuroimmunology, vol. 148, no. 1-2, pp. 146–153, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. A. V. Rao and L. G. Rao, “Carotenoids and human health,” Pharmacological Research, vol. 55, no. 3, pp. 207–216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. C. Ramassamy, “Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets,” European Journal of Pharmacology, vol. 545, no. 1, pp. 51–64, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. L. Gan and L. Mucke, “Paths of convergence: sirtuins in aging and neurodegeneration,” Neuron, vol. 58, no. 1, pp. 10–14, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Reinke and Z. Fabry, “Breaking or making immunological privilege in the central nervous system: the regulation of immunity by neuropeptides,” Immunology Letters, vol. 104, no. 1-2, pp. 102–109, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. B. Engelhardt and R. M. Ransohoff, “The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms,” Trends in Immunology, vol. 26, no. 9, pp. 485–495, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Sardi, L. Zambusi, A. Finardi et al., “Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis,” Journal of Neuroimmunology, vol. 271, no. 1-2, pp. 18–29, 2014. View at Publisher · View at Google Scholar · View at Scopus
  82. N. M. Sherwood, S. L. Krueckl, and J. E. McRory, “The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily,” Endocrine Reviews, vol. 21, no. 6, pp. 619–670, 2000. View at Publisher · View at Google Scholar
  83. M. Delgado, D. Pozo, and D. Ganea, “The significance of vasoactive intestinal peptide in immunomodulation,” Pharmacological Reviews, vol. 56, no. 2, pp. 249–290, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Ster, F. De Bock, N. C. Guérineau et al., “Exchange protein activated by cAMP (EPAC) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 7, pp. 2519–2524, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. A. P. Barrie, A. M. Clohessy, C. S. Buensuceso, M. V. Rogers, and J. M. Allen, “Pituitary adenylyl cyclase-activating peptide stimulates extracellular signal-regulated kinase 1 or 2 (ERK1/2) activity in a Ras-independent, mitogen-activated protein kinase/ERK kinase 1 or 2-dependent manner in PC12 cells,” The Journal of Biological Chemistry, vol. 272, no. 32, pp. 19666–19671, 1997. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Villalba, J. Bockaert, and L. Journot, “Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway,” The Journal of Neuroscience, vol. 17, no. 1, pp. 83–90, 1997. View at Google Scholar · View at Scopus
  87. V. Lelièvre, N. Pineau, J. Du et al., “Differential effects of peptide histidine isoleucine (PHI) and related peptides on stimulation and suppression of neuroblastoma cell proliferation. A novel VIP-independent action of PHI via MAP kinase,” The Journal of Biological Chemistry, vol. 273, no. 31, pp. 19685–19690, 1998. View at Publisher · View at Google Scholar · View at Scopus
  88. D. Spengler, C. Waeber, C. Pantaloni et al., “Differential signal transduction by five splice variants of the PACAP receptor,” Nature, vol. 365, no. 6442, pp. 170–175, 1993. View at Publisher · View at Google Scholar · View at Scopus
  89. S. G. Straub and G. W. G. Sharp, “A wortmannin-sensitive signal transduction pathway is involved in the stimulation of insulin release by vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide,” The Journal of Biological Chemistry, vol. 271, no. 3, pp. 1660–1668, 1996. View at Publisher · View at Google Scholar · View at Scopus
  90. K. S. Murthy, K. M. Zhang, J. G. Jin, J. R. Grider, and G. M. Makhlouf, “VIP-mediated G protein-coupled Ca2+ influx activates a constitutive NOS in dispersed gastric muscle cells,” American Journal of Physiology, vol. 265, no. 4, part 1, pp. G660–G671, 1993. View at Google Scholar
  91. S.-W. M. Koh, “Signal transduction through the vasoactive intestinal peptide receptor stimulates phosphorylation of the tyrosine kinase pp60c-src,” Biochemical and Biophysical Research Communications, vol. 174, no. 2, pp. 452–458, 1991. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Delgado and D. Ganea, “Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit interleukin-12 transcription by regulating nuclear factor κB and Ets activation,” The Journal of Biological Chemistry, vol. 274, no. 45, pp. 31930–31940, 1999. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Delgado and D. Ganea, “Inhibition of IFN-γ-induced Janus kinase-1-STAT1 activation in macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide,” Journal of Immunology, vol. 165, no. 6, pp. 3051–3057, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Delgado and D. Ganea, “Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions,” Amino Acids, vol. 45, no. 1, pp. 25–39, 2013. View at Publisher · View at Google Scholar · View at Scopus
  95. J. A. Waschek, “VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair,” British Journal of Pharmacology, vol. 169, no. 3, pp. 512–523, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. A. Chorny, E. Gonzalez-Rey, A. Fernandez-Martin, D. Ganea, and M. Delgado, “Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response,” Blood, vol. 107, no. 9, pp. 3787–3794, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. M. G. Toscano, M. Delgado, W. Kong, F. Martin, M. Skarica, and D. Ganea, “Dendritic cells transduced with lentiviral vectors expressing vip differentiate into vip-secreting tolerogenic-like DCs,” Molecular Therapy, vol. 18, no. 5, pp. 1035–1045, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. D. K. Litwin, A. K. Wilson, and S. I. Said, “Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro,” Regulatory Peptides, vol. 40, no. 1, pp. 63–74, 1992. View at Publisher · View at Google Scholar · View at Scopus
  99. J. R. Temerozo, R. Joaquim, E. G. Regis, W. Savino, and D. C. Bou-Habib, “Macrophage resistance to HIV-1 infection is enhanced by the neuropeptides VIP and PACAP,” PLoS ONE, vol. 8, no. 6, Article ID e67701, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Ichinose, M. Asai, and M. Sawada, “Activation of outward current by pituitary adenylate cyclase activating polypeptide in mouse microglial cells,” Journal of Neuroscience Research, vol. 51, no. 3, pp. 382–390, 1998. View at Google Scholar · View at Scopus
  101. W.-K. Kim, D. Ganea, and G. M. Jonakait, “Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10,” Journal of Neuroimmunology, vol. 126, no. 1-2, pp. 16–24, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. W.-K. Kim, Y. Kan, D. Ganea, R. P. Hart, I. Gozes, and G. M. Jonakait, “Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-α production in injured spinal cord and in activated microglia via a cAMP-dependent pathway,” Journal of Neuroscience, vol. 20, no. 10, pp. 3622–3630, 2000. View at Google Scholar · View at Scopus
  103. M. Delgado, G. M. Jonakait, and D. Ganea, “Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit chemokine production in activated microglia,” Glia, vol. 39, no. 2, pp. 148–161, 2002. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Delgado, J. Leceta, and D. Ganea, “Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia,” Journal of Leukocyte Biology, vol. 73, no. 1, pp. 155–164, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Delgado, “Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in endotoxin-activated microglia,” Biochemical and Biophysical Research Communications, vol. 293, no. 2, pp. 771–776, 2002. View at Publisher · View at Google Scholar · View at Scopus
  106. M. Delgado, “Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit CBP-NF-κB interaction in activated microglia,” Biochemical and Biophysical Research Communications, vol. 297, no. 5, pp. 1181–1185, 2002. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Nishimoto, H. Miyakawa, K. Wada, and A. Furuta, “Activation of the VIP/VPAC2 system induces reactive astrocytosis associated with increased expression of glutamate transporters,” Brain Research, vol. 1383, pp. 43–53, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Delgado and D. Ganea, “Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma,” The FASEB Journal, vol. 17, no. 13, pp. 1922–1924, 2003. View at Publisher · View at Google Scholar
  109. M. Delgado and D. Ganea, “Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation,” The FASEB Journal, vol. 17, no. 8, pp. 944–946, 2003. View at Google Scholar · View at Scopus
  110. M. Song, J.-X. Xiong, Y.-Y. Wang, J. Tang, B. Zhang, and Y. Bai, “VIP enhances phagocytosis of fibrillar beta-amyloid by microglia and attenuates amyloid deposition in the brain of APP/PS1 mice,” PLoS ONE, vol. 7, no. 2, Article ID e29790, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. R. P. Gomariz, I. Gutiérrez-Cañas, A. Arranz et al., “Peptides targeting toll-like receptor signalling pathways for novel immune therapeutics,” Current Pharmaceutical Design, vol. 16, no. 9, pp. 1063–1080, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. R. P. Gomariz, A. Arranz, C. Abad et al., “Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP,” Journal of Leukocyte Biology, vol. 78, no. 2, pp. 491–502, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. N. Foster, S. R. Lea, P. M. Preshaw, and J. J. Taylor, “Pivotal advance: vasoactive intestinal peptide inhibits up-regulation of human monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages,” Journal of Leukocyte Biology, vol. 81, no. 4, pp. 893–903, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. X. Jiang, S. A. McClellan, R. P. Barrett, Y. Zhang, and L. D. Hazlett, “Vasoactive intestinal peptide downregulates proinflammatory TLRs while upregulating anti-inflammatory TLRs in the infected cornea,” Journal of Immunology, vol. 189, no. 1, pp. 269–278, 2012. View at Publisher · View at Google Scholar · View at Scopus
  115. I. Gutiérrez-Cañas, Y. Juarranz, B. Santiago et al., “VIP down-regulates TLR4 expression and TLR4-mediated chemokine production in human rheumatoid synovial fibroblasts,” Rheumatology, vol. 45, no. 5, pp. 527–532, 2006. View at Publisher · View at Google Scholar · View at Scopus
  116. D. Offen, Y. Sherki, E. Melamed, M. Fridkin, D. E. Brenneman, and I. Gozes, “Vasoactive intestinal peptide (VIP) prevents neurotoxicity in neuronal cultures: relevance to neuroprotection in Parkinson's disease,” Brain Research, vol. 854, no. 1-2, pp. 257–262, 2000. View at Publisher · View at Google Scholar · View at Scopus
  117. N. Fujimori, T. Oono, H. Igarashi et al., “Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase,” Peptides, vol. 32, no. 10, pp. 2067–2076, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. E. Vacas, A. M. Bajo, A. V. Schally, M. Sánchez-Chapado, J. C. Prieto, and M. J. Carmena, “Antioxidant activity of vasoactive intestinal peptide in HK2 human renal cells,” Peptides, vol. 38, no. 2, pp. 275–281, 2012. View at Publisher · View at Google Scholar · View at Scopus
  119. R. Yu, H. Zhang, L. Huang, X. Liu, and J. Chen, “Anti-hyperglycemic, antioxidant and anti-inflammatory effects of VIP and a VPAC1 agonist on streptozotocin-induced diabetic mice,” Peptides, vol. 32, no. 2, pp. 216–222, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. N. Tunçel, O. T. Korkmaz, N. Tekin, E. Şener, F. Akyüz, and M. Inal, “Antioxidant and anti-apoptotic activity of Vasoactive Intestinal Peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum,” Journal of Molecular Neuroscience, vol. 46, no. 1, pp. 51–57, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. L. Mester, K. Kovacs, B. Racz et al., “Pituitary adenylate cyclase-activating polypeptide is protective against oxidative stress in human retinal pigment epithelial cells,” Journal of Molecular Neuroscience, vol. 43, no. 1, pp. 35–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. G. Horvath, R. Brubel, K. Kovacs et al., “Effects of PACAP on oxidative stress-induced cell death in rat kidney and human hepatocyte cells,” Journal of Molecular Neuroscience, vol. 43, no. 1, pp. 67–75, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. O. Masmoudi-Kouki, S. Douiri, Y. Hamdi et al., “Pituitary adenylate cyclase-activating polypeptide protects astroglial cells against oxidative stress-induced apoptosis,” Journal of Neurochemistry, vol. 117, no. 3, pp. 403–411, 2011. View at Publisher · View at Google Scholar · View at Scopus
  124. H. Ohtaki, A. Satoh, T. Nakamachi et al., “Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor,” Journal of Molecular Neuroscience, vol. 42, no. 3, pp. 397–403, 2010. View at Publisher · View at Google Scholar · View at Scopus
  125. P. Szakaly, E. Laszlo, K. Kovacs et al., “Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) show increased susceptibility to in vivo renal ischemia/reperfusion injury,” Neuropeptides, vol. 45, no. 2, pp. 113–121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  126. R. A. Stetler, Y. Gao, R. S. Zukin et al., “Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 7, pp. 3204–3209, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. D. M. Basso, M. S. Beattie, and J. C. Bresnahan, “Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection,” Experimental Neurology, vol. 139, no. 2, pp. 244–256, 1996. View at Publisher · View at Google Scholar · View at Scopus
  128. K.-M. Fang, J.-K. Chen, S.-C. Hung et al., “Effects of combinatorial treatment with pituitary adenylate cyclase activating peptide and human mesenchymal stem cells on spinal cord tissue repair,” PLoS ONE, vol. 5, no. 12, Article ID e15299, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. C. Brifault, M. Gras, D. Liot, V. May, D. Vaudry, and O. Wurtz, “Delayed pituitary adenylate cyclase-activating polypeptide delivery after brain stroke improves functional recovery by inducing M2 microglia/macrophage polarization,” Stroke, vol. 46, no. 2, pp. 520–528, 2014. View at Publisher · View at Google Scholar · View at Scopus
  130. T. Nakamachi, M. Tsuchida, N. Kagami et al., “IL-6 and PACAP receptor expression and localization after global brain ischemia in mice,” Journal of Molecular Neuroscience, vol. 48, no. 3, pp. 518–525, 2012. View at Publisher · View at Google Scholar · View at Scopus
  131. R. Nunan, H. Sivasathiaseelan, D. Khan, M. Zaben, and W. Gray, “Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release,” Glia, vol. 62, no. 8, pp. 1313–1327, 2014. View at Publisher · View at Google Scholar · View at Scopus
  132. F. A. Russell, “Calcitonin gene-related peptide: physiology and pathophysiology,” Physiological Reviews, vol. 94, no. 4, pp. 1099–1142, 2014. View at Publisher · View at Google Scholar · View at Scopus
  133. D. R. Poyner, P. M. Sexton, I. Marshall et al., “International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors,” Pharmacological Reviews, vol. 54, no. 2, pp. 233–246, 2002. View at Publisher · View at Google Scholar · View at Scopus
  134. L. M. McLatchie, N. J. Fraser, M. J. Main et al., “RAMPS regulate the transport and ligand specificity of the calcitonin- receptor-like receptor,” Nature, vol. 393, no. 6683, pp. 333–339, 1998. View at Publisher · View at Google Scholar · View at Scopus
  135. B. N. Evans, M. I. Rosenblatt, L. O. Mnayer, K. R. Oliver, and I. M. Dickerson, “CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors,” The Journal of Biological Chemistry, vol. 275, no. 40, pp. 31438–31443, 2000. View at Publisher · View at Google Scholar · View at Scopus
  136. S. C. Egea and I. M. Dickerson, “Direct interactions between calcitonin-like receptor (CLR) and CGRP-receptor component protein (RCP) regulate CGRP receptor signaling,” Endocrinology, vol. 153, no. 4, pp. 1850–1860, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. D. L. Hay, D. R. Poyner, and D. M. Smith, “Desensitisation of adrenomedullin and CGRP receptors,” Regulatory Peptides, vol. 112, no. 1–3, pp. 139–145, 2003. View at Publisher · View at Google Scholar · View at Scopus
  138. S. D. Brain and A. D. Grant, “Vascular actions of calcitonin gene-related peptide and adrenomedullin,” Physiological Reviews, vol. 84, no. 3, pp. 903–934, 2004. View at Publisher · View at Google Scholar · View at Scopus
  139. H. Drissi, F. Lasmoles, V. L. Mellay, P. J. Marie, and M. Lieberherr, “Activation of phospholipase C-β1 via Gα(q/11) during calcium mobilization by calcitonin gene-related peptide,” The Journal of Biological Chemistry, vol. 273, no. 32, pp. 20168–20174, 1998. View at Publisher · View at Google Scholar · View at Scopus
  140. H. Drissi, M. Lieberherr, M. Hott, P. J. Marie, and F. Lasmoles, “Calcitonin gene-related peptide (CGRP) increases intracellular free Ca2+ concentrations but not cyclic AMP formation in CGRP receptor-positive osteosarcoma cells (OHS-4),” Cytokine, vol. 11, no. 3, pp. 200–207, 1999. View at Publisher · View at Google Scholar · View at Scopus
  141. S. Morara, L.-P. Wang, V. Filippov et al., “Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices,” European Journal of Neuroscience, vol. 28, no. 11, pp. 2213–2220, 2008. View at Publisher · View at Google Scholar · View at Scopus
  142. Z. Wang, W. Ma, J.-G. Chabot, and R. Quirion, “Calcitonin gene-related peptide as a regulator of neuronal CaMKII-CREB, microglial p38-NFκB and astroglial ERK-Stat1/3 cascades mediating the development of tolerance to morphine-induced analgesia,” Pain, vol. 151, no. 1, pp. 194–205, 2010. View at Publisher · View at Google Scholar · View at Scopus
  143. M. E. Bigal, S. Walter, and A. M. Rapoport, “Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development,” Headache, vol. 53, no. 8, pp. 1230–1244, 2013. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Evangelista, “Role of calcitonin gene-related peptide in gastric mucosal defence and healing,” Current Pharmaceutical Design, vol. 15, no. 30, pp. 3571–3576, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Dakhama, G. L. Larsen, and E. W. Gelfand, “Calcitonin gene-related peptide: role in airway homeostasis,” Current Opinion in Pharmacology, vol. 4, no. 3, pp. 215–220, 2004. View at Publisher · View at Google Scholar · View at Scopus
  146. A.-G. Lafont, Y.-F. Wang, G.-D. Chen et al., “Involvement of calcitonin and its receptor in the control of calcium-regulating genes and calcium homeostasis in zebrafish (Danio rerio),” Journal of Bone and Mineral Research, vol. 26, no. 5, pp. 1072–1083, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. P. Holzer, “Neurogenic vasodilatation and plasma leakage in the skin,” General Pharmacology, vol. 30, no. 1, pp. 5–11, 1998. View at Publisher · View at Google Scholar · View at Scopus
  148. A. C. Raddant and A. F. Russo, “Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation,” Expert Reviews in Molecular Medicine, vol. 13, article e36, 2011. View at Publisher · View at Google Scholar · View at Scopus
  149. R. N. Gomes, H. C. Castro-Faria-Neto, P. T. Bozza et al., “Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia,” Shock, vol. 24, no. 6, pp. 590–594, 2005. View at Publisher · View at Google Scholar · View at Scopus
  150. I. Kroeger, A. Erhardt, D. Abt et al., “The neuropeptide calcitonin gene-related peptide (CGRP) prevents inflammatory liver injury in mice,” Journal of Hepatology, vol. 51, no. 2, pp. 342–353, 2009. View at Publisher · View at Google Scholar · View at Scopus
  151. M. Levite, “Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 21, pp. 12544–12549, 1998. View at Publisher · View at Google Scholar · View at Scopus
  152. Y. Umeda, M. Takamiya, H. Yoshizaki, and M. Arisawa, “Inhibition of mitogen-stimulated T lymphocyte proliferation by calcitonin gene-related peptide,” Biochemical and Biophysical Research Communications, vol. 154, no. 1, pp. 227–235, 1988. View at Publisher · View at Google Scholar · View at Scopus
  153. J. P. McGillis, S. Humphreys, V. Rangnekar, and J. Ciallella, “Modulation of B lymphocyte differentiation by calcitonin gene-related peptide (CGRP). II. Inhibition of LPS-induced kappa light chain expression by CGRP,” Cellular Immunology, vol. 150, no. 2, pp. 405–416, 1993. View at Publisher · View at Google Scholar · View at Scopus
  154. S. Fernandez, M. A. Knopf, and J. P. McGillis, “Calcitonin-gene related peptide (CGRP)inhibits interleukin-7-induced pre-B cell colony formation,” Journal of Leukocyte Biology, vol. 67, no. 5, pp. 669–676, 2000. View at Google Scholar · View at Scopus
  155. W. Ding, L. L. Stohl, J. A. Wagner, and R. D. Granstein, “Calcitonin gene-related peptide biases langerhans cells toward Th2-type immunity,” The Journal of Immunology, vol. 181, no. 9, pp. 6020–6026, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. M. Baliu-Piqué, G. Jusek, and B. Holzmann, “Neuroimmunological communication via CGRP promotes the development of a regulatory phenotype in TLR4-stimulated macrophages,” European Journal of Immunology, vol. 44, no. 12, pp. 3708–3716, 2014. View at Publisher · View at Google Scholar
  157. A. Consonni, S. Morara, F. Codazzi, F. Grohovaz, and D. Zacchetti, “Inhibition of lipopolysaccharide-induced microglia activation by calcitonin gene related peptide and adrenomedullin,” Molecular and Cellular Neuroscience, vol. 48, no. 2, pp. 151–160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  158. H. Li, M. L. Cuzner, and J. Newcombe, “Microglia-derived macrophages in early multiple sclerosis plaques,” Neuropathology and Applied Neurobiology, vol. 22, no. 3, pp. 207–215, 1996. View at Publisher · View at Google Scholar · View at Scopus
  159. F. W. Gay, T. J. Drye, G. W. A. Dick, and M. M. Esiri, “The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis: identification and characterization of the primary demyelinating lesion,” Brain, vol. 120, no. 8, pp. 1461–1483, 1997. View at Publisher · View at Google Scholar · View at Scopus
  160. C. Trebst, T. Lykke Sørensen, P. Kivisäkk et al., “CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis,” The American Journal of Pathology, vol. 159, no. 5, pp. 1701–1710, 2001. View at Publisher · View at Google Scholar
  161. M. M. Ayers, L. J. Hazelwood, D. V. Catmull et al., “Early glial responses in murine models of multiple sclerosis,” Neurochemistry International, vol. 45, no. 2-3, pp. 409–419, 2004. View at Publisher · View at Google Scholar · View at Scopus
  162. M. D. Harzenetter, A. R. Novotny, P. Gais, C. A. Molina, F. Altmayr, and B. Holzmann, “Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER,” The Journal of Immunology, vol. 179, no. 1, pp. 607–615, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. C. Schaeffer, D. Vandroux, L. Thomassin, P. Athias, L. Rochette, and J.-L. Connat, “Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1643, no. 1–3, pp. 65–73, 2003. View at Publisher · View at Google Scholar · View at Scopus
  164. S. Sueur, M. Pesant, L. Rochette, and J.-L. Connat, “Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex,” Journal of Molecular and Cellular Cardiology, vol. 39, no. 6, pp. 955–963, 2005. View at Publisher · View at Google Scholar · View at Scopus
  165. Z. Zhou, C.-P. Hu, C.-J. Wang, T.-T. Li, J. Peng, and Y.-J. Li, “Calcitonin gene-related peptide inhibits angiotensin II-induced endothelial progenitor cells senescence through up-regulation of klotho expression,” Atherosclerosis, vol. 213, no. 1, pp. 92–101, 2010. View at Publisher · View at Google Scholar · View at Scopus
  166. N. A. Umoh, R. K. Walker, R. M. Millis et al., “Calcitonin gene-related peptide regulates cardiomyocyte survival through regulation of oxidative stress by PI3K/Akt and MAPK signaling pathways,” Annals of Clinical and Experimental Hypertension, vol. 2, no. 1, pp. 1007–1023, 2014. View at Google Scholar
  167. R. Huang, A. Karve, I. Shah et al., “Deletion of the mouse α-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia-reperfusion injury,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 294, no. 3, pp. H1291–H1297, 2008. View at Publisher · View at Google Scholar · View at Scopus
  168. L. Yang, T. Sakurai, A. Kamiyoshi et al., “Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury,” Journal of Molecular and Cellular Cardiology, vol. 59, pp. 55–66, 2013. View at Publisher · View at Google Scholar · View at Scopus
  169. S.-J. Smillie, R. King, X. Kodji et al., “An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress,” Hypertension, vol. 63, no. 5, pp. 1056–1062, 2014. View at Publisher · View at Google Scholar · View at Scopus
  170. S. Hinuma, H. Onda, and M. Fujino, “The quest for novel bioactive peptides utilizing orphan seven-transmembrane-domain receptors,” Journal of Molecular Medicine, vol. 77, no. 6, pp. 495–504, 1999. View at Publisher · View at Google Scholar · View at Scopus
  171. Y. Habata, R. Fujii, M. Hosoya et al., “Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum,” Biochimica et Biophysica Acta, vol. 1452, no. 1, pp. 25–35, 1999. View at Publisher · View at Google Scholar · View at Scopus
  172. M. Hosoya, Y. Kawamata, S. Fukusumi et al., “Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin,” The Journal of Biological Chemistry, vol. 275, no. 28, pp. 21061–21067, 2000. View at Publisher · View at Google Scholar · View at Scopus
  173. B. Masri, B. Knibiehler, and Y. Audigier, “Apelin signalling: a promising pathway from cloning to pharmacology,” Cellular Signalling, vol. 17, no. 4, pp. 415–426, 2005. View at Publisher · View at Google Scholar · View at Scopus
  174. N. De Mota, Z. Lenkei, and C. Llorens-Cortès, “Cloning, pharmacological characterization and brain distribution of the rat apelin receptor,” Neuroendocrinology, vol. 72, no. 6, pp. 400–407, 2000. View at Publisher · View at Google Scholar · View at Scopus
  175. A.-M. O'Carroll, T. L. Selby, M. Palkovits, and S. J. Lolait, “Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues,” Biochimica et Biophysica Acta—Gene Structure and Expression, vol. 1492, no. 1, pp. 72–80, 2000. View at Publisher · View at Google Scholar · View at Scopus
  176. E. Devic, L. Paquereau, P. Vernier, B. Knibiehler, and Y. Audigier, “Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis,” Mechanisms of Development, vol. 59, no. 2, pp. 129–140, 1996. View at Publisher · View at Google Scholar · View at Scopus
  177. S. D. Katugampola, J. J. Maguire, S. R. Matthewson, and A. P. Davenport, “[125I]-(Pyr1)Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man,” British Journal of Pharmacology, vol. 132, no. 6, pp. 1255–1260, 2001. View at Publisher · View at Google Scholar · View at Scopus
  178. H. Choe, M. Farzan, M. Konkel et al., “The orphan seven-transmembrane receptor Apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1,” Journal of Virology, vol. 72, no. 7, pp. 6113–6118, 1998. View at Google Scholar · View at Scopus
  179. A. Folino, P. G. Montarolo, M. Samaja, and R. Rastaldo, “Effects of apelin on the cardiovascular system,” Heart Failure Reviews, vol. 20, no. 4, pp. 505–518, 2015. View at Publisher · View at Google Scholar
  180. Y. Yang, S.-Y. Lv, S.-K. Lyu, D. Wu, and Q. Chen, “The protective effect of apelin on ischemia/reperfusion injury,” Peptides, vol. 63, pp. 43–46, 2015. View at Publisher · View at Google Scholar · View at Scopus
  181. J. Kim, “Apelin-APJ signaling: a potential therapeutic target for pulmonary arterial hypertension,” Molecules and Cells, vol. 37, no. 3, pp. 196–201, 2014. View at Publisher · View at Google Scholar · View at Scopus
  182. S.-Y. Lv, Y.-J. Yang, and Q. Chen, “Regulation of feeding behavior, gastrointestinal function and fluid homeostasis by apelin,” Peptides, vol. 44, pp. 87–92, 2013. View at Publisher · View at Google Scholar · View at Scopus
  183. W. Choe, A. Albright, J. Sulcove et al., “Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells,” Journal of NeuroVirology, vol. 6, no. 1, pp. S61–S69, 2000. View at Publisher · View at Google Scholar · View at Scopus
  184. B. Masri, H. Lahlou, H. Mazarguil, B. Knibiehler, and Y. Audigier, “Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein,” Biochemical and Biophysical Research Communications, vol. 290, no. 1, pp. 539–545, 2002. View at Publisher · View at Google Scholar · View at Scopus
  185. Q. Xin, B. Cheng, Y. Pan et al., “Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation,” Peptides, vol. 63, pp. 55–62, 2015. View at Publisher · View at Google Scholar · View at Scopus
  186. O. Pisarenko, V. Shulzhenko, I. Studneva et al., “Structural apelin analogues: mitochondrial ROS inhibition and cardiometabolic protection in myocardial ischaemia reperfusion injury,” British Journal of Pharmacology, vol. 172, no. 12, pp. 2933–2945, 2015. View at Publisher · View at Google Scholar
  187. E. Thornton and R. Vink, “Treatment with a substance p receptor antagonist is neuroprotective in the intrastriatal 6-hydroxydopamine model of early parkinson's disease,” PLoS ONE, vol. 7, no. 4, Article ID e34138, 2012. View at Publisher · View at Google Scholar · View at Scopus