Table of Contents Author Guidelines Submit a Manuscript
The Scientific World Journal
Volume 2012, Article ID 905785, 11 pages
http://dx.doi.org/10.1100/2012/905785
Review Article

Do β-Defensins and Other Antimicrobial Peptides Play a Role in Neuroimmune Function and Neurodegeneration?

1Department of Biological Sciences, Case Western Reserve University, Cleveland, OH 44106, USA
2Department of Pathology, University of Maryland, Baltimore, MD 20742, USA
3UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA
4Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA

Received 24 June 2011; Accepted 26 October 2011

Academic Editor: R. E. Tanzi

Copyright © 2012 Wesley M. Williams 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. J. A. Fernández, L. Rojo, R. O. Kuljis, and R. B. Maccioni, “The damage signals hypothesis of Alzheimer's disease pathogenesis,” Journal of Alzheimer's Disease, vol. 14, no. 3, pp. 329–333, 2008. View at Google Scholar · View at Scopus
  2. R. B. Maccioni, L. E. Rojo, J. A. Fernández, and R. O. Kuljis, “The role of neuroimmunomodulation in Alzheimer's disease,” Annals of the New York Academy of Sciences, vol. 1153, pp. 240–246, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. T. S. McCormick and A. Weinberg, “Epithelial cell-derived antimicrobial peptides are multifunctional agents that bridge innate and adaptive immunity,” Periodontology 2000, vol. 54, no. 1, pp. 195–206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. D. M. Laube, S. Yim, L. K. Ryan, K. O. Kisich, and G. Diamond, “Antimicrobial peptides in the airway,” Current Topics in Microbiology and Immunology, vol. 306, pp. 153–182, 2006. View at Google Scholar · View at Scopus
  5. W. M. Williams, “Microvascular function and inflammation in the senescent, neurodegenerative, and traumatized brain,” in Microcirculation: Function, Malfunction and Measurement, pp. 1–208, NOVA Science Publishers, Hauppauge, NY, USA, 2009. View at Google Scholar
  6. S. Rivest, “Regulation of innate immune responses in the brain,” Nature Reviews Immunology, vol. 9, no. 6, pp. 429–439, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. S. van Watering, P. J. Sterk, K. F. Rabe, and P. S. Hiemstra, “Defensins: key players or bystanders in infection, injury, and repair in the lung?” Journal of Allergy and Clinical Immunology, vol. 104, no. 6, pp. 1131–1138, 1999. View at Google Scholar · View at Scopus
  8. C. Auvynet and Y. Rosenstein, “Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity,” FEBS Journal, vol. 276, no. 22, pp. 6497–6508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. H.-N. Hao, J. Zhao, G. Lotoczky, W. E. Grever, and W. D. Lyman, “Induction of human β-defensin-2 expression in human astrocytes by lipopolysaccharide and cytokines,” Journal of Neurochemistry, vol. 77, no. 4, pp. 1027–1035, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. P. Bergman, S. Termén, L. Johansson et al., “The antimicrobial peptide rCRAMP is present in the central nervous system of the rat,” Journal of Neurochemistry, vol. 93, no. 5, pp. 1132–1140, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Ø. Pedersen, A. Larsen, M. Stoltenberg, and M. Penkowa, “Cell death in the injured brain: roles of metallothioneins,” Progress in Histochemistry and Cytochemistry, vol. 44, no. 1, pp. 1–27, 2009. View at Publisher · View at Google Scholar
  12. M. Letiembre, Y. Liu, S. Walter et al., “Screening of innate immune receptors in neurodegenerative diseases: a similar pattern,” Neurobiology of Aging, vol. 30, no. 5, pp. 759–768, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. N. L. Sparkman and R. W. Johnson, “Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress,” NeuroImmunoModulation, vol. 15, no. 4–6, pp. 323–330, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Beauquis, F. Homo-Delarche, Y. Revsin, A. F. de Nicola, and F. Saravia, “Brain alterations in autoimmune and pharmacological models of diabetes mellitus: focus on hypothalamic-pituitary-adrenocortical axis disturbances,” NeuroImmunoModulation, vol. 15, no. 1, pp. 61–67, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. H. P. Jia, J. N. Mills, F. Barahmand-Pour et al., “Molecular cloning and characterization of rat genes encoding homologues of human β-defensins,” Infection and Immunity, vol. 67, no. 9, pp. 4827–4833, 1999. View at Google Scholar · View at Scopus
  16. L.-O. Brandenburg, D. Varoga, N. Nicolaeva et al., “Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis,” Journal of Neuropathology and Experimental Neurology, vol. 67, no. 11, pp. 1041–1054, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. C. van den Heuvel, E. Thornton, and R. Vink, “Traumatic brain injury and Alzheimer's disease: a review,” Progress in Brain Research, vol. 161, pp. 303–316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. Z. Ahmed, D. Baker, and M. L. Cuzner, “Interleukin-12 induces mild experimental allergic encephalomyelitis following local central nervous system injury in the Lewis rat,” Journal of Neuroimmunology, vol. 140, no. 1-2, pp. 109–117, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Inglese, E. Bomsztyk, O. Gonen, L. J. Mannon, R. I. Grossman, and H. Rusinek, “Dilated perivascular spaces: hallmarks of mild traumatic brain injury,” American Journal of Neuroradiology, vol. 26, no. 4, pp. 719–724, 2005. View at Google Scholar · View at Scopus
  20. K. Kinoshita, K. Chatzipanteli, E. Vitarbo et al., “Interleukin-1β messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature,” Neurosurgery, vol. 51, no. 1, pp. 195–203, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Utagawa, J. S. Truettner, W. D. Dietrich, and H. M. Bramlett, “Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats,” Experimental Neurology, vol. 211, no. 1, pp. 283–291, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. E. A. Vitarbo, K. Chatzipanteli, K. Kinoshita, J. S. Truettner, O. F. Alonso, and W. D. Dietrich, “Tumor necrosis factor α expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature,” Neurosurgery, vol. 55, no. 2, pp. 416–424, 2004. View at Google Scholar · View at Scopus
  23. A. Baroni, G. Donnarumma, I. Paoletti et al., “Antimicrobial human β-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells,” Peptides, vol. 30, no. 2, pp. 267–272, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. R. Mahida and R. N. Cunliffe, “Defensins and mucosal protection,” Novartis Foundation Symposium, vol. 263, pp. 71–77, 2004. View at Google Scholar · View at Scopus
  25. L. Yin and B. A. Dale, “Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human β-defensin-2,” Journal of Medical Microbiology, vol. 56, part 7, pp. 976–987, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. K. F. Neumann, L. Rojo, L. P. Navarrete, G. Farías, P. Reyes, and R. B. Maccioni, “Insulin resistance and Alzheimer's disease: molecular links & clinical implications,” Current Alzheimer's Research, vol. 5, no. 5, pp. 438–447, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. W. Duan, Z. Guo, H. Jiang, M. Ware, X. J. Li, and M. P. Mattson, “Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 5, pp. 2911–2916, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. J. S. Roriz-Filho, T. M. Sa-Roriz, I. Rosset et al., “(Pre)diabetes, brain aging, and cognition,” Biochimica et Biophysica Acta, vol. 1792, no. 5, pp. 432–443, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Zhang, B. S. Pan, B. Zhao, L. M. Zhang, Y. L. Huang, and F. Y. Sun, “Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of β-secretase activation and β-amyloid generation in rat brains,” Neuroscience, vol. 161, no. 4, pp. 1045–1056, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. G. J. Biessels, S. Staekenborg, E. Brunner, C. Brayne, and P. Scheltens, “Risk of dementia in diabetes mellitus: a systematic review,” Lancet Neurology, vol. 5, no. 1, pp. 64–74, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. Z. H. He, X. G. Zhi, X. C. Sun, and W. Y. Tang, “Correlation analysis of increased blood glucose and insulin resistance after traumatic brain injury in rats,” Nan Fang Yi Ke Da Xue Xue Bao, vol. 27, no. 3, pp. 315–317, 2007. View at Google Scholar · View at Scopus
  32. E. Andresen, G. Günther, J. Bullwinkel, C. Lange, and H. Heine, “Increased expression of β-defensin 1 (DEFB1) in chronic obstructive pulmonary disease,” PLoS ONE, vol. 6, no. 7, pp. 1–10, 2011. View at Publisher · View at Google Scholar
  33. D. M. Bowdish, D. J. Davidson, and R. E. Hancock, “Immunomodulatory properties of defensins and cathelicidins,” Current Topics in Microbiology and Immunology, vol. 306, pp. 27–66, 2006. View at Google Scholar · View at Scopus
  34. G. Münch, D. Schicktanz, A. Behme et al., “Amino acid specificity of glycation and protein-AGE crosslinking reactivities determined with a dipeptide SPOT library,” Nature Biotechnology, vol. 17, no. 10, pp. 1006–1010, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. S. David and A. Kroner, “Repertoire of microglial and macrophage responses after spinal cord injury,” Nature Reviews Neuroscience, vol. 12, no. 7, pp. 388–399, 2011. View at Publisher · View at Google Scholar
  36. M. F. Gregor and G. S. Hotamisligil, “Inflammatory mechanisms in obesity,” Annual Review of Immunology, vol. 29, pp. 415–445, 2011. View at Publisher · View at Google Scholar
  37. B. E. Leonard, “Inflammation, depression and dementia: are they connected?” Neurochemical Research, vol. 32, no. 10, pp. 1749–1756, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Nakabayashi, S. Suzaki, and H. Tomita, “Neural injury and recovery near cortical contusions: a clinical magnetic resonance spectroscopy study,” Journal of Neurosurgery, vol. 106, no. 3, pp. 370–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Bondanelli, L. de Marinis, M. R. Ambrosio et al., “Occurrence of pituitary dysfunction following traumatic brain injury,” Journal of Neurotrauma, vol. 21, no. 6, pp. 685–696, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Marklund, K. Salci, G. Ronquist, and L. Hillered, “Energy metabolic changes in the early post-injury period following traumatic brain injury in rats,” Neurochemical Research, vol. 31, no. 8, pp. 1085–1093, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. E. Park, S. McKnight, J. Ai, and A. J. Baker, “Purkinje cell vulnerability to mild and severe forebrain head trauma,” Journal of Neuropathology and Experimental Neurology, vol. 65, no. 3, pp. 226–234, 2006. View at Google Scholar · View at Scopus
  42. K. Nakayama, N. Okamura, H. Arai, K. Sekizawa, and H. Sasaki, “Expression of human β-defensin-1 in the choroid plexus,” Annals of Neurology, vol. 45, no. 5, p. 685, 1999. View at Publisher · View at Google Scholar · View at Scopus
  43. N. K. Phulwani and T. Kielian, “Poly (ADP-ribose) polymerases (PARPs) 1–3 regulate astrocyte activation,” Journal of Neurochemistry, vol. 106, no. 2, pp. 578–590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Kipp, A. Norkute, S. Johann et al., “Brain-region-specific astroglial responses in vitro after LPS exposure,” Journal of Molecular Neuroscience, vol. 35, no. 2, pp. 235–243, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Gurley, J. Nichols, S. Liu, N. K. Phulwani, N. Esen, and T. Kielian, “Microglia and astrocyte activation by toll-like receptor ligands: modulation by PPAR-γ agonists,” PPAR Research, vol. 2008, Article ID 453120, 15 pages, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. L. Walter and H. Neumann, “Role of microglia in neuronal degeneration and regeneration,” Seminars in Immunopathology, vol. 31, no. 4, pp. 513–525, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Farina, F. Aloisi, and E. Meinl, “Astrocytes are active players in cerebral innate immunity,” Trends in Immunology, vol. 28, no. 3, pp. 138–145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. N. P. Hailer, “Immunosuppression after traumatic or ischemic CNS damage: it is neuroprotective and illuminates the role of microglial cells,” Progress in Neurobiology, vol. 84, no. 3, pp. 211–233, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. W. H. Hoffman, M. F. Casanova, C. D. Cudrici et al., “Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis,” Experimental and Molecular Pathology, vol. 83, no. 1, pp. 65–72, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. M. D. Laird, J. R. Vender, and K. M. Dhandapani, “Opposing roles for reactive astrocytes following traumatic brain injury,” NeuroSignals, vol. 16, no. 2-3, pp. 154–164, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. D. E. Boddie, D. G. Currie, O. Eremin, and S. D. Heys, “Immune suppression and isolated severe head injury: a significant clinical problem,” British Journal of Neurosurgery, vol. 17, no. 5, pp. 405–417, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. O. J. Schiepers, M. C. Wichers, and M. Maes, “Cytokines and major depression,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 29, no. 2, pp. 201–217, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. D. van West and M. Maes, “Activation of the inflammatory response system: a new look at the etiopathogenesis of major depression,” Neuroendocrinology Letters, vol. 20, no. 1-2, pp. 11–17, 1999. View at Google Scholar · View at Scopus
  54. H. J. Jeong, S.-H. Hong, Y.-C. Nam et al., “The effect of acupuncture on proinflammatory cytokine production in patients with chronic headache: a preliminary report,” American Journal of Chinese Medicine, vol. 31, no. 6, pp. 945–954, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. P. M. Lenzlinger, V. H. J. Hans, H. I. Joller-Jemelka, O. Trentz, M. C. Morganti-Kossmann, and T. Kossmann, “Markers for cell-mediated immune response are elevated in cerebrospinal fluid and serum after severe traumatic brain injury in humans,” Journal of Neurotrauma, vol. 18, no. 5, pp. 479–490, 2001. View at Google Scholar · View at Scopus
  56. R. Adam, D. Rüssing, O. Adams et al., “Role of human brain microvascular endothelial cells during central nervous system infection,” Thrombosis and Haemostasis, vol. 94, no. 2, pp. 341–346, 2005. View at Publisher · View at Google Scholar
  57. M. C. Morganti-Kossmann, L. Satgunaseelan, N. Bye, and T. Kossmann, “Modulation of immune response by head injury,” Injury, vol. 38, no. 12, pp. 1392–1400, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Kalla, Z. Liu, S. Xu et al., “Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice,” Journal of Comparative Neurology, vol. 436, no. 2, pp. 182–201, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. M. C. Morganti-Kossmann, M. Rancan, V. I. Otto, P. F. Stahel, and T. Kossmann, “Role of cerebral inflammation after traumatic brain injury: a revisited concept,” Shock, vol. 16, no. 3, pp. 165–177, 2001. View at Google Scholar · View at Scopus
  60. K. Kamm, W. Vanderkolk, C. Lawrence, M. Jonker, and A. T. Davis, “The effect of traumatic brain injury upon the concentration and expression of interleukin-1β and interleukin-10 in the rat,” The Journal of Trauma, vol. 60, no. 1, pp. 152–157, 2006. View at Google Scholar · View at Scopus
  61. A. Rasley, S. L. Tranguch, D. M. Rati, and I. Marriott, “Murine glia express the immunosuppressive cytokine, interleukin-10, following exposure to Borrelia burgdorferi or Neisseria meningitidis,” Glia, vol. 53, no. 6, pp. 583–592, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Kamada, F. Yu, C. Nito, and P. H. Chan, “Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood-brain barrier dysfunction,” Stroke, vol. 38, no. 3, pp. 1044–1049, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Israelsson, H. Bengtsson, A. Kylberg et al., “Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury,” Journal of Neurotrauma, vol. 25, no. 8, pp. 959–974, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Knieriem, C. M. Otto, and D. Macintire, “Hyperglycemia in critically ill patients,” Compendium: Continuing Education For Veterinarians, vol. 29, no. 6, pp. 360–362, 2007. View at Google Scholar · View at Scopus
  65. B. Young, L. Ott, R. Dempsey, D. Haack, and P. Tibbs, “Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients,” Annals of Surgery, vol. 210, no. 4, pp. 466–472, 1989. View at Google Scholar · View at Scopus
  66. A. Cochran, E. R. Scaife, K. W. Hansen, and E. C. Downey, “Hyperglycemia and outcomes from pediatric traumatic brain injury,” Journal of Trauma, vol. 55, no. 6, pp. 1035–1038, 2003. View at Google Scholar · View at Scopus
  67. A. Prakash and B. F. Matta, “Hyperglycaemia and neurological injury,” Current Opinion in Anaesthesiology, vol. 21, no. 5, pp. 565–569, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. E. Jeremitsky, L. A. Omert, C. M. Dunham, J. Wilberger, and A. Rodriguez, “The impact of hyperglycemia on patients with severe brain injury,” Journal of Trauma—Injury, Infection and Critical Care, vol. 58, no. 1, pp. 47–50, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. L. Lazar, I. Erez, M. Gutermacher, and S. Katz, “Brain concussion produces transient hypokalemia in children,” Journal of Pediatric Surgery, vol. 32, no. 1, pp. 88–90, 1997. View at Publisher · View at Google Scholar · View at Scopus
  70. C. E. Dixon, B. G. Lyeth, and J. T. Povlishock, “A fluid percussion model of experimental brain injury in the rat,” Journal of Neurosurgery, vol. 67, no. 1, pp. 110–119, 1987. View at Google Scholar
  71. T. Otori, J. C. Friedland, G. Sinson, T. K. McIntosh, R. Raghupathi, and F. A. Welsh, “Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat brain,” Journal of Neurotrauma, vol. 21, no. 6, pp. 707–718, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. J. L. Sperry, H. L. Frankel, S. L. Vanek et al., “Early hyperglycemia predicts multiple organ failure and mortality but not infection,” The Journal of Trauma, vol. 63, no. 3, pp. 487–493, 2007. View at Google Scholar · View at Scopus
  73. A. M. Laird, P. R. Miller, P. D. Kilgo, J. W. Meredith, and M. C. Chang, “Relationship of early hyperglycemia to mortality in trauma patients,” The Journal of Trauma, vol. 56, no. 5, pp. 1058–1062, 2004. View at Google Scholar · View at Scopus
  74. B. Avants, J. T. Duda, J. Kim et al., “Multivariate analysis of structural and diffusion imaging in traumatic brain injury,” Academic Radiology, vol. 15, no. 11, pp. 1360–1375, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. M. R. Viant, B. G. Lyeth, M. G. Miller, and R. F. Berman, “An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model,” NMR in Biomedicine, vol. 18, no. 8, pp. 507–516, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Levine, E. Fujiwara, C. O'Connor et al., “In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging,” Journal of Neurotrauma, vol. 23, no. 10, pp. 1396–1411, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. N. Kagansky, S. Levy, and H. Knobler, “The role of hyperglycemia in acute stroke,” Archives of Neurology, vol. 58, no. 8, pp. 1209–1212, 2001. View at Google Scholar · View at Scopus
  78. B. Lin, M. D. Ginsberg, and R. Busto, “Hyperglycemic exacerbation of neuronal damage following forebrain ischemia: microglial, astrocytic and endothelial alterations,” Acta Neuropathologica, vol. 96, no. 6, pp. 610–620, 1998. View at Publisher · View at Google Scholar · View at Scopus
  79. E. V. Valore, C. H. Park, A. J. Quayle, K. R. Wiles, P. B. McCray Jr, and T. Ganz, “Human β-defensin-1: an antimicrobial peptide of urogenital tissues,” Journal of Clinical Investigation, vol. 101, no. 8, pp. 1633–1642, 1998. View at Google Scholar · View at Scopus
  80. J. Harder, J. Bartels, E. Christophers, and J. M. Schroder, “A peptide antibiotic from human skin,” Nature, vol. 387, no. 6636, p. 861, 1997. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Harder, U. Meyer-Hoffert, L. M. Teran et al., “Mucoid Pseudomonas aeruginosa, TNF-α, and IL-1β, but not IL-6, induce human β-defensin-2 in respiratory epithelia,” American Journal of Respiratory Cell and Molecular Biology, vol. 22, no. 6, pp. 714–721, 2000. View at Google Scholar · View at Scopus
  82. M. Mathews, H. P. Jia, J. M. Guthmiller et al., “Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands,” Infection and Immunity, vol. 67, no. 6, pp. 2740–2745, 1999. View at Google Scholar · View at Scopus
  83. C. Zhao, I. Wang, and R. I. Lehrer, “Widespread expression of β-defensin hBD-1 in human secretory glands and epithelial cells,” FEBS Letters, vol. 396, no. 2-3, pp. 319–322, 1996. View at Publisher · View at Google Scholar · View at Scopus
  84. F. Niyonsaba, H. Ushio, N. Nakano et al., “Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines,” Journal of Investigative Dermatology, vol. 127, no. 3, pp. 594–604, 2007. View at Publisher · View at Google Scholar
  85. A. M. McDermott, “The role of antimicrobial peptides at the ocular surface,” Ophthalmic Research, vol. 41, no. 2, pp. 60–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. D. Yang, O. Chertov, S. N. Bykovskaia et al., “β-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6,” Science, vol. 286, no. 5439, pp. 525–528, 1999. View at Publisher · View at Google Scholar · View at Scopus
  87. Z. Wu, D. M. Hoover, D. Yang et al., “Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human β-defensin-3,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8880–8885, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. D. M. Hoover, C. Boulègue, D. Yang et al., “The structure of human macrophage inflammatory protein-3α/CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human β-defensins,” Journal of Biological Chemistry, vol. 277, no. 40, pp. 37647–37654, 2002. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Röhrl, D. Yang, J. J. Oppenheim, and T. Hehlgans, “Human β-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2,” Journal of Immunology, vol. 184, no. 12, pp. 6688–6694, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. G. Flynn, S. Maru, J. Loughlin, I. A. Romero, and D. Male, “Regulation of chemokine receptor expression in human microglia and astrocytes,” Journal of Neuroimmunology, vol. 136, no. 1-2, pp. 84–93, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. N. Tanuma, H. Sakuma, A. Sasaki, and Y. Matsumoto, “Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis,” Acta neuropathologica, vol. 112, no. 2, pp. 195–204, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. O. Froy, A. Hananel, N. Chapnik, and Z. Madar, “Differential effect of insulin treatment on decreased levels of β-defensins and toll-like receptors in diabetic rats,” Molecular Immunology, vol. 44, no. 5, pp. 796–802, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. T. Hiratsuka, M. Nakazato, Y. Date, H. Mukae, and S. Matsukura, “Nucleotide sequence and expression of rat β-defensin-1: its significance in diabetic rodent models,” Nephron, vol. 88, no. 1, pp. 65–70, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. K. G. Kohlgraf, L. C. Pingel, D. E. Dietrich, and K. A. Brogden, “Defensins as anti-inflammatory compounds and mucosal adjuvants,” Future Microbiology, vol. 5, no. 1, pp. 99–113, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. Z. Tiszlavicz, V. Endrész, B. Németh et al., “Inducible expression of human β-defensin 2 by Chlamydophila pneumoniae in brain capillary endothelial cells,” Innate Immunity, vol. 17, no. 5, pp. 463–469, 2011. View at Publisher · View at Google Scholar
  96. F. Niyonsaba, H. Ushio, I. Nagaoka, K. Okumura, and H. Ogawa, “The human β-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes,” Journal of Immunology, vol. 175, no. 3, pp. 1776–1784, 2005. View at Google Scholar · View at Scopus
  97. G. Donnarumma, I. Paoletti, E. Buommino et al., “Anti-inflammatory effects of moxifloxacin and human β-defensin 2 association in human lung epithelial cell line (A549) stimulated with lipopolysaccharide,” Peptides, vol. 28, no. 12, pp. 2286–2292, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. Q. Shu, Z. Shi, Z. Y. Zhao et al., “Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of β-defensin-2 in rats,” Shock, vol. 26, no. 4, pp. 365–371, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Frye, J. Bargon, and R. Gropp, “Expression of human β-defensin-1 promotes differentiation of keratinocytes,” Journal of Molecular Medicine, vol. 79, no. 5-6, pp. 275–282, 2001. View at Publisher · View at Google Scholar · View at Scopus
  100. O. N. Kokiko-Cochran, M. P. Michaels, and R. J. Hamm, “Delayed glucose treatment improves cognitive function following fluid-percussion injury,” Neuroscience Letters, vol. 436, no. 1, pp. 27–30, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Barnea, Z. Madar, and O. Froy, “Glucose and insulin are needed for optimal defensin expression in human cell lines,” Biochemical and Biophysical Research Communications, vol. 367, no. 2, pp. 452–456, 2008. View at Publisher · View at Google Scholar
  102. A. N. Malik and G. Al-Kafaji, “Glucose regulation of β-defensin-1 mRNA in human renal cells,” Biochemical and Biophysical Research Communications, vol. 353, no. 2, pp. 318–323, 2007. View at Publisher · View at Google Scholar
  103. T. Matsuda, Y. Murata, N. Kawamura et al., “Selective induction of α 1 isoform of (Na++K+)-ATPase by insulin/insulin-like growth factor-1 in cultured rat astrocytes,” Archives of Biochemistry and Biophysics, vol. 307, no. 1, pp. 175–182, 1993. View at Google Scholar
  104. J. M. Ruiz-Albusac, E. Velazquez, J. Iglesias, E. Jimenez, and E. Blazquez, “Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured rat astroglial cells,” Journal of Neurochemistry, vol. 68, no. 1, pp. 10–19, 1997. View at Google Scholar · View at Scopus
  105. J. V. Kim and M. L. Dustin, “Innate response to focal necrotic injury inside the blood-brain barrier,” Journal of Immunology, vol. 177, no. 8, pp. 5269–5277, 2006. View at Google Scholar · View at Scopus
  106. J. Falsig, P. Porzgen, S. Lund, A. Schrattenholz, and M. Leist, “The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function,” Journal of Neurochemistry, vol. 96, no. 3, pp. 893–907, 2006. View at Publisher · View at Google Scholar
  107. N. T. Mowery, O. L. Gunter, O. Guillamondegui et al., “Stress insulin resistance is a marker for mortality in traumatic brain injury,” The Journal of Trauma, vol. 66, no. 1, pp. 145–153, 2009. View at Google Scholar · View at Scopus
  108. M. Buczek, J. Alvarez, J. Azhar et al., “Delayed changes in regional brain energy metabolism following cerebral concussion in rats,” Metabolic Brain Disease, vol. 17, no. 3, pp. 153–167, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. A. B. J. Groeneveld, A. Beishuizen, and F. C. Visser, “Insulin: a wonder drug in the critically ill?” Critical Care, vol. 6, no. 2, pp. 102–105, 2002. View at Google Scholar · View at Scopus
  110. S. E. Zulian, M. G. I. de Boschero, and N. M. Giusto, “Insulin action on polyunsaturated phosphatidic acid formation in rat brain: an “in vitro” model with synaptic endings from cerebral cortex and hippocampus,” Neurochemical Research, vol. 34, no. 7, pp. 1236–1248, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. Ø. Hundal, “Major depressive disorder viewed as a dysfunction in astroglial bioenergetics,” Medical Hypotheses, vol. 68, no. 2, pp. 370–377, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. Q. Wan, Z. G. Xiong, H. Y. Man et al., “Recruitment of functional GABAA receptors to postsynaptic domains by insulin,” Nature, vol. 388, no. 6643, pp. 686–690, 1997. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Wang, R. Wang, Z. Zhao et al., “Coexistences of insulin signaling-related proteins and choline acetyltransferase in neurons,” Brain Research, vol. 1249, pp. 237–243, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. R. Tehranian, M. E. Rose, V. Vagni et al., “Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury,” Journal of Neurotrauma, vol. 25, no. 7, pp. 755–767, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. A. C. Conti, R. Raghupathi, J. Q. Trojanowski, and T. K. McIntosh, “Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period,” Journal of Neuroscience, vol. 18, no. 15, pp. 5663–5672, 1998. View at Google Scholar · View at Scopus
  116. R. Raghupathi, A. C. Conti, D. I. Graham et al., “Mild traumatic brain injury induces apoptotic cell death in the cortex that is preceded by decreases in cellular Bcl-2 immunoreactivity,” Neuroscience, vol. 110, no. 4, pp. 605–616, 2002. View at Publisher · View at Google Scholar · View at Scopus
  117. I. Nagaoka, F. Niyonsaba, Y. Tsutsumi-Ishii, H. Tamura, and M. Hirata, “Evaluation of the effect of human β-defensins on neutrophil apoptosis,” International Immunology, vol. 20, no. 4, pp. 543–553, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. A. Säljö, F. Bao, A. Hamberger, K. G. Haglid, and H. A. Hansson, “Exposure to short-lasting impulse noise causes microglial and astroglial cell activation in the adult rat brain,” Pathophysiology, vol. 8, no. 2, pp. 105–111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  119. D. J. Myer, G. G. Gurkoff, S. M. Lee, D. A. Hovda, and M. V. Sofroniew, “Essential protective roles of reactive astrocytes in traumatic brain injury,” Brain, vol. 129, no. 10, pp. 2761–2772, 2006. View at Publisher · View at Google Scholar · View at Scopus
  120. M. L. Block and J. S. Hong, “Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism,” Progress in Neurobiology, vol. 76, no. 2, pp. 77–98, 2005. View at Publisher · View at Google Scholar · View at Scopus
  121. S. M. Lucas, N. J. Rothwell, and R. M. Gibson, “The role of inflammation in CNS injury and disease,” British Journal of Pharmacology, vol. 147, supplement 1, pp. S232–S240, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. Z. Q. Xiong, W. Qian, K. Suzuki, and J. O. McNamara, “Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration,” Journal of Neuroscience, vol. 23, no. 3, pp. 955–960, 2003. View at Google Scholar · View at Scopus
  123. G. Trendelenburg, “Acute neurodegeneration and the inflammasome: central processor for danger signals and the inflammatory response?” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 5, pp. 867–881, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. R. M. Steinman and H. Hemmi, “Dendritic cells: translating innate to adaptive immunity,” Current Topics in Microbiology and Immunology, vol. 311, pp. 17–58, 2006. View at Google Scholar
  125. R. M. Steinman and J. Banchereau, “Taking dendritic cells into medicine,” Nature, vol. 449, no. 7161, pp. 419–426, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. S. J. van Vliet, J. D. Dunnen, S. I. Gringhuis, T. B. Geijtenbeek, and Y. van Kooyk, “Innate signaling and regulation of dendritic cell immunity,” Current Opinion in Immunology, vol. 19, no. 4, pp. 435–440, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. E. J. McMahon, S. L. Bailey, and S. D. Miller, “CNS dendritic cells: critical participants in CNS inflammation?” Neurochemistry International, vol. 49, no. 2, pp. 195–203, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. P. Iribarren, Y.-H. Cui, Y. Le, and J. M. Wang, “The role of dendritic cells in neurodegenerative diseases,” Archivum Immunologiae et Therapiae Experimentalis, vol. 50, no. 3, pp. 187–196, 2002. View at Google Scholar
  129. A. Ciaramella, F. Bizzoni, F. Salani et al., “Increased pro-inflammatory response by dendritic cells from patients with Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 559–572, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. H.-G. Fischer and G. Reichmann, “Brain dendritic cells and macrophages/microglia in central nervous system inflammation,” Journal of Immunology, vol. 166, no. 4, pp. 2717–2726, 2001. View at Google Scholar · View at Scopus
  131. J. Karman, C. Ling, M. Sandor, and Z. Fabry, “Dendritic cells in the initiation of immune responses against central nervous system-derived antigens,” Immunology Letters, vol. 92, no. 1-2, pp. 107–115, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. A. L. Zozulya, S. Ortler, J. E. Lee et al., “Intracerebral dendritic cells critically modulate encephalitogenic versus regulatory immune responses in the CNS,” Journal of Neuroscience, vol. 29, no. 1, pp. 140–152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  133. C.-F. Calvo, E. Amigou, C. Desaymard, and J. Glowinski, “A pro- and an anti-inflammatory cytokine are synthesized in distinct brain macrophage cells during innate activation,” Journal of Neuroimmunology, vol. 170, no. 1-2, pp. 21–30, 2005. View at Google Scholar
  134. M. Pashenkov, N. Teleshova, and H. Link, “Inflammation in the central nervous system: the role for dendritic cells,” Brain Pathology, vol. 13, no. 1, pp. 23–33, 2003. View at Google Scholar · View at Scopus
  135. B. Ludewig, B. Odermatt, S. Landmann, H. Hengartner, and R. M. Zinkernagel, “Dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissue,” Journal of Experimental Medicine, vol. 188, no. 8, pp. 1493–1501, 1998. View at Publisher · View at Google Scholar · View at Scopus
  136. F. Sallusto and A. Lanzavecchia, “Mobilizing dendritic cells for tolerance, priming, and chronic inflammation,” Journal of Experimental Medicine, vol. 189, no. 4, pp. 611–614, 1999. View at Publisher · View at Google Scholar · View at Scopus
  137. R. E. W. Hancock and H. G. Sahl, “Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies,” Nature Biotechnology, vol. 24, no. 12, pp. 1551–1557, 2006. View at Publisher · View at Google Scholar · View at Scopus
  138. O. Joffre, M. A. Nolte, R. Sporri, and C. R. E. Sousa, “Inflammatory signals in dendritic cell activation and the induction of adaptive immunity,” Immunological Reviews, vol. 227, no. 1, pp. 234–247, 2009. View at Publisher · View at Google Scholar
  139. M. A. Hölzl, J. Hofer, P. Steinberger, K. Pfistershammer, and G. J. Zlabinger, “Host antimicrobial proteins as endogenous immunomodulators,” Immunology Letters, vol. 119, no. 1-2, pp. 4–11, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. D. Yang, A. Biragyn, L. W. Kwak, and J. J. Oppenheim, “Mammalian defensins in immunity: more than just microbicidal,” Trends in Immunology, vol. 23, no. 6, pp. 291–296, 2002. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Röhrl, D. Yang, J. J. Oppenheim, and T. Hehlgans, “Identification and biological characterization of mouse β-defensin 14, the orthologue of human β-defensin 3,” Journal of Biological Chemistry, vol. 283, no. 9, pp. 5414–5419, 2008. View at Publisher · View at Google Scholar · View at Scopus
  142. D. J. Davidson, A. J. Currie, G. S. D. Reid et al., “The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization,” Journal of Immunology, vol. 172, no. 2, pp. 1146–1156, 2004. View at Google Scholar · View at Scopus
  143. L. Hao, J. Wang, Z. Zou et al., “Transplantation of BMSCs expressing hPDGF-A/hBD2 promotes wound healing in rats with combined radiation-wound injury,” Gene Therapy, vol. 16, no. 1, pp. 34–42, 2009. View at Publisher · View at Google Scholar · View at Scopus
  144. L. C. Pingel, K. G. Kohlgraf, C. J. Hansen, C. G. Eastman, D. E. Dietrich, and K. K. Burnell, “Human β-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesion from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response,” Immunology and Cell Biology, vol. 86, pp. 643–649, 2008. View at Google Scholar
  145. F. Semple, H. Macpherson, S. Webb et al., “Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF,” European Journal of Immunology, vol. 41, no. 11, pp. 3291–3300, 2011. View at Publisher · View at Google Scholar
  146. A. Biragyn, M. Coscia, K. Nagashima, M. Sanford, H. A. Young, and P. Olkhanud, “Murine β-defensin 2 promotes TLR-4/MyD88-mediated and NF-κB-dependent atypical death of APCs via activation of TNFR2,” Journal of Leukocyte Biology, vol. 83, no. 4, pp. 998–1008, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. S. J. Soscia, J. E. Kirby, K. J. Washicosky et al., “The Alzheimer's disease-associated amyloid β-protein is an antimicrobial peptide,” PLoS ONE, vol. 5, no. 3, Article ID e9505, 2010. View at Publisher · View at Google Scholar · View at Scopus
  148. D. M. Hoover, K. R. Rajashankar, R. Blumenthal et al., “The structure of human β-defensin-2 shows evidence of higher order oligomerization,” Journal of Biological Chemistry, vol. 275, no. 42, pp. 32911–32918, 2000. View at Google Scholar · View at Scopus
  149. C. Auvynet, C. El Amri, C. Lacombe et al., “Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9,” FEBS Journal, vol. 275, no. 16, pp. 4134–4151, 2008. View at Publisher · View at Google Scholar · View at Scopus
  150. R. Saravanan and S. Bhattacharjya, “Oligomeric structure of a cathelicidin antimicrobial peptide in dodecylphosphocholine micelle determination by NMR spectroscopy,” Biochimica et Biophysica Acta, vol. 1808, no. 1, pp. 369–381, 2011. View at Publisher · View at Google Scholar