Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2016, Article ID 6986175, 17 pages
http://dx.doi.org/10.1155/2016/6986175
Research Article

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
2Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

Received 9 May 2016; Revised 18 October 2016; Accepted 7 November 2016

Academic Editor: Soh Yamazaki

Copyright © 2016 Carolina Cunha 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. F. Vilhardt, “Microglia: phagocyte and glia cell,” International Journal of Biochemistry and Cell Biology, vol. 37, no. 1, pp. 17–21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Nimmerjahn, F. Kirchhoff, and F. Helmchen, “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
  3. 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
  4. C. S. McKimmie, D. Roy, T. Forster, and J. K. Fazakerley, “Innate immune response gene expression profiles of N9 microglia are pathogen-type specific,” Journal of Neuroimmunology, vol. 175, no. 1-2, pp. 128–141, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. V. H. Perry and V. O'Connor, “The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective,” ASN Neuro, vol. 2, no. 5, Article ID e00047, 2010. View at Google Scholar · View at Scopus
  6. M. B. Graeber and W. J. Streit, “Microglia: biology and pathology,” Acta Neuropathologica, vol. 119, no. 1, pp. 89–105, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Brites and A. R. Vaz, “Microglia centered pathogenesis in ALS: insights in cell interconnectivity,” Frontiers in Cellular Neuroscience, vol. 8, no. MAY, article 117, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Fernandes, L. Miller-Fleming, and T. F. Pais, “Microglia and inflammation: conspiracy, controversy or control?” Cellular and Molecular Life Sciences, vol. 71, no. 20, pp. 3969–3985, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Ohsawa and S. Kohsaka, “Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brain,” GLIA, vol. 59, no. 12, pp. 1793–1799, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. G. K. Sheridan and K. J. Murphy, “Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage,” Open Biology, vol. 3, no. 12, Article ID 130181, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. A. E. Cardona, E. P. Pioro, M. E. Sasse et al., “Control of microglial neurotoxicity by the fractalkine receptor,” Nature Neuroscience, vol. 9, no. 7, pp. 917–924, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. B. A. Durafourt, C. S. Moore, D. A. Zammit et al., “Comparison of polarization properties of human adult microglia and blood-derived macrophages,” Glia, vol. 60, no. 5, pp. 717–727, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. V. Chhor, T. Le Charpentier, S. Lebon et al., “Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia In vitro,” Brain, Behavior, and Immunity, vol. 32, pp. 70–85, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. H.-C. Liu, M.-H. Zheng, Y.-L. Du et al., “N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli,” Cellular Immunology, vol. 278, no. 1-2, pp. 84–90, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. H.-T. Zhu, C. Bian, J.-C. Yuan et al., “Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury,” Journal of Neuroinflammation, vol. 11, article 59, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. J. G. Walsh, D. A. Muruve, and C. Power, “Inflammasomes in the CNS,” Nature Reviews Neuroscience, vol. 15, no. 2, pp. 84–97, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. B. Lu, H. Wang, U. Andersson, and K. J. Tracey, “Regulation of HMGB1 release by inflammasomes,” Protein and Cell, vol. 4, no. 3, pp. 163–167, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. J. S. Park, D. Svetkauskaite, Q. He et al., “Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein,” Journal of Biological Chemistry, vol. 279, no. 9, pp. 7370–7377, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. R. Hanayama, M. Tanaka, K. Miwa, A. Shinohara, A. Iwamatsu, and S. Nagata, “Identification of a factor that links apoptotic cells to phagocytes,” Nature, vol. 417, no. 6885, pp. 182–187, 2002. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Righi, L. Mori, G. De Libero et al., “Monokine production by microglial cell clones,” European Journal of Immunology, vol. 19, no. 8, pp. 1443–1448, 1989. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Nikodemova and J. J. Watters, “Outbred ICR/CD1 mice display more severe neuroinflammation mediated by microglial TLR4/CD14 activation than inbred C57Bl/6 mice,” Neuroscience, vol. 190, pp. 67–74, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. R. W. Freilich, M. E. Woodbury, and T. Ikezu, “Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia,” PLoS ONE, vol. 8, no. 11, Article ID e79416, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. X. He, Z. Jing, and G. Cheng, “MicroRNAs: new regulators of Toll-like receptor signalling pathways,” BioMed Research International, vol. 2014, Article ID 945169, 14 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. E. D. Ponomarev, T. Veremeyko, and H. L. Weiner, “MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS,” GLIA, vol. 61, no. 1, pp. 91–103, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Jiang, Y. Xiang, D. Wang et al., “Dysregulated expression of miR-146a contributes to age-related dysfunction of macrophages,” Aging Cell, vol. 11, no. 1, pp. 29–40, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Veremeyko, S. Siddiqui, I. Sotnikov, A. Yung, and E. D. Ponomarev, “IL-4/IL-13-dependent and independent expression of miR-124 and its contribution to M2 phenotype of monocytic cells in normal conditions and during allergic inflammation,” PLOS ONE, vol. 8, no. 12, Article ID e81774, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. D. Brites and A. Fernandes, “Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation,” Frontiers in Cellular Neuroscience, vol. 9, article no. 476, pp. 1–20, 2015. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Aryani and B. Denecke, “Exosomes as a nanodelivery system: a key to the future of neuromedicine?” Molecular Neurobiology, vol. 53, no. 2, pp. 818–834, 2016. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Gustin, M. Kirchmeyer, E. Koncina et al., “NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes,” PLoS ONE, vol. 10, no. 6, Article ID e0130624, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. S. M. Burm, E. A. Zuiderwijk-Sick, A. E. J. T Jong et al., “Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases,” Journal of Neuroscience, vol. 35, no. 2, pp. 678–687, 2015. View at Publisher · View at Google Scholar · View at Scopus
  31. D. J. Ksiazek-Winiarek, M. J. Kacperska, and A. Glabinski, “MicroRNAs as novel regulators of neuroinflammation,” Mediators of inflammation, vol. 2013, Article ID 172351, 11 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Alexander, R. Hu, M. C. Runtsch et al., “Exosome-delivered microRNAs modulate the inflammatory response to endotoxin,” Nature Communications, vol. 6, article 7321, 2015. View at Publisher · View at Google Scholar · View at Scopus
  33. Y.-H. Cui, Y. Le, W. Gong et al., “Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine microglial cells,” The Journal of Immunology, vol. 168, no. 1, pp. 434–442, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Barateiro, A. R. Vaz, S. L. Silva, A. Fernandes, and D. Brites, “ER stress, mitochondrial dysfunction and calpain/JNK activation are involved in oligodendrocyte precursor cell death by unconjugated bilirubin,” NeuroMolecular Medicine, vol. 14, no. 4, pp. 285–302, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Barateiro, V. E. Miron, S. D. Santos et al., “Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination,” Molecular neurobiology, vol. 47, no. 2, pp. 632–644, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. A. L. Cardoso, J. R. Guedes, L. Pereira de Almeida, and M. C. Pedroso de Lima, “miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production,” Immunology, vol. 135, no. 1, pp. 73–88, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Fernandes, A. S. Falcão, R. F. M. Silva et al., “Inflammatory signalling pathways involved in astroglial activation by unconjugated bilirubin,” Journal of Neurochemistry, vol. 96, no. 6, pp. 1667–1679, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. D. Kurpius, N. Wilson, L. Fuller, A. Hoffman, and M. E. Dailey, “Early activation, motility, and homing of neonatal microglia to injured neurons does not require protein synthesis,” GLIA, vol. 54, no. 1, pp. 58–70, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Caldeira, A. F. Oliveira, C. Cunha et al., “Microglia change from a reactive to an age-like phenotype with the time in culture,” Frontiers in Cellular Neuroscience, vol. 8, article no. 152, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. S. L. Silva, C. Osório, A. R. Vaz et al., “Dynamics of neuron-glia interplay upon exposure to unconjugated bilirubin,” Journal of Neurochemistry, vol. 117, no. 3, pp. 412–424, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. S. L. Silva, A. R. Vaz, A. Barateiro et al., “Features of bilirubin-induced reactive microglia: from phagocytosis to inflammation,” Neurobiology of Disease, vol. 40, no. 3, pp. 663–675, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Fernandes, A. S. Falcão, R. F. M. Silva, M. A. Brito, and D. Brites, “MAPKs are key players in mediating cytokine release and cell death induced by unconjugated bilirubin in cultured rat cortical astrocytes,” European Journal of Neuroscience, vol. 25, no. 4, pp. 1058–1068, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Wang, S. Zhang, J. Weber, D. Baxter, and D. J. Galas, “Export of microRNAs and microRNA-protective protein by mammalian cells,” Nucleic Acids Research, vol. 38, no. 20, pp. 7248–7259, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. W. J. Streit, S. A. Walter, and N. A. Pennell, “Reactive microgliosis,” Progress in Neurobiology, vol. 57, no. 6, pp. 563–581, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Mashimo, N. Ohguro, S. Nomura, N. Hashida, K. Nakai, and Y. Tano, “Neutrophil chemotaxis and local expression of interleukin-10 in the tolerance of endotoxin-induced uveitis,” Investigative Ophthalmology and Visual Science, vol. 49, no. 12, pp. 5450–5457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. I. Napoli and H. Neumann, “Microglial clearance function in health and disease,” Neuroscience, vol. 158, no. 3, pp. 1030–1038, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. F. G. Bauernfeind, G. Horvath, A. Stutz et al., “Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression,” The Journal of Immunology, vol. 183, no. 2, pp. 787–791, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. R. T. Liu, A. Wang, E. To et al., “Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells,” Experimental Eye Research, vol. 127, pp. 49–58, 2014. View at Publisher · View at Google Scholar · View at Scopus
  49. 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
  50. A. Falcão, L. A. R. Carvalho, G. Lidónio et al., “Dipeptidyl vinyl sulfone as a novel chemical tool to inhibit HMGB1/NLRP3-inflammasome and inflamma-miRs in Aβ-mediated microglial inflammation,” ACS Chemical Neuroscience, 2016. View at Publisher · View at Google Scholar
  51. A. Halle, V. Hornung, G. C. Petzold et al., “The NALP3 inflammasome is involved in the innate immune response to amyloid-β,” Nature Immunology, vol. 9, no. 8, pp. 857–865, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Fanjul-Fernández, A. R. Folgueras, S. Cabrera, and C. López-Otín, “Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1803, no. 1, pp. 3–19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. H.-M. Gao, H. Zhou, F. Zhang, B. C. Wilson, W. Kam, and J.-S. Hong, “HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration,” Journal of Neuroscience, vol. 31, no. 3, pp. 1081–1092, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. J.-B. Kim, S. C. Joon, Y.-M. Yu et al., “HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain,” Journal of Neuroscience, vol. 26, no. 24, pp. 6413–6421, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. J.-B. Kim, C.-M. Lim, Y.-M. Yu, and J.-K. Lee, “Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain,” Journal of Neuroscience Research, vol. 86, no. 5, pp. 1125–1131, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Wu, C. Cerutti, M. A. Lopez-Ramirez et al., “Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation,” Journal of Cerebral Blood Flow and Metabolism, vol. 35, no. 3, pp. 412–423, 2015. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Zhao, L. Zhang, G. Lian et al., “Sildenafil attenuates LPS-induced pro-inflammatory responses through down-regulation of intracellular ROS-related MAPK/NF-κB signaling pathways in N9 microglia,” International Immunopharmacology, vol. 11, no. 4, pp. 468–474, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. G. Zhang, J.-L. He, X.-Y. Xie, and C. Yu, “LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways,” International Journal of Molecular Medicine, vol. 30, no. 3, pp. 561–568, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. X. Lu, L. Ma, L. Ruan et al., “Resveratrol differentially modulates inflammatory responses of microglia and astrocytes,” Journal of Neuroinflammation, vol. 7, article 46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. A. J. Bruce-Keller, J. L. Keeling, J. N. Keller, F. F. Huang, S. Camondola, and M. P. Mattson, “Antiinflammatory effects of estrogen on microglial activation,” Endocrinology, vol. 141, no. 10, pp. 3646–3656, 2000. View at Google Scholar · View at Scopus
  61. R. Shechter, O. Miller, G. Yovel et al., “Recruitment of Beneficial M2 Macrophages to Injured Spinal Cord Is Orchestrated by Remote Brain Choroid Plexus,” Immunity, vol. 38, no. 3, pp. 555–569, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. E. W. G. M. Boddeke, I. Meigel, S. Frentzel, K. Biber, L. Q. Renn, and P. Gebicke-Härter, “Functional expression of the fractalkine (CX3C) receptor and its regulation by lipopolysaccharide in rat microglia,” European Journal of Pharmacology, vol. 374, no. 2, pp. 309–313, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Pachot, M.-A. Cazalis, F. Venet et al., “Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as new feature of sepsis-induced immunosuppression,” Journal of Immunology, vol. 180, no. 9, pp. 6421–6429, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Jose, S. W. Tan, Y. Y. Ooi, R. Ramasamy, and S. Vidyadaran, “Mesenchymal stem cells exert anti-proliferative effect on lipopolysaccharide-stimulated BV2 microglia by reducing tumour necrosis factor-α levels,” Journal of Neuroinflammation, vol. 11, no. 1, article 149, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Chen, W. Jalabi, K. B. Shpargel et al., “Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4,” Journal of Neuroscience, vol. 32, no. 34, pp. 11706–11715, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. T. Li, S. Pang, Y. Yu, X. Wu, J. Guo, and S. Zhang, “Proliferation of parenchymal microglia is the main source of microgliosis after ischaemic stroke,” Brain: A Journal Of Neurology, vol. 136, pp. 3578–3588, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. A. G. Orr, A. L. Orr, X.-J. Li, R. E. Gross, and S. F. Traynelis, “Adenosine A2A receptor mediates microglial process retraction,” Nature Neuroscience, vol. 12, no. 7, pp. 872–878, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. S. E. Haynes, G. Hollopeter, G. Yang et al., “The P2Y12 receptor regulates microglial activation by extracellular nucleotides,” Nature Neuroscience, vol. 9, no. 12, pp. 1512–1519, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Honda, Y. Sasaki, K. Ohsawa et al., “Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors,” The Journal of Neuroscience, vol. 21, no. 6, pp. 1975–1982, 2001. View at Google Scholar · View at Scopus
  70. S. Lively and L. C. Schlichter, “The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion,” Journal of Neuroinflammation, vol. 10, article 75, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. H. Scheiblich, F. Roloff, V. Singh, M. Stangel, M. Stern, and G. Bicker, “Nitric oxide/cyclic GMP signaling regulates motility of a microglial cell line and primary microglia in vitro,” Brain Research, vol. 1564, pp. 9–21, 2014. View at Publisher · View at Google Scholar · View at Scopus
  72. A. A. Babcock, W. A. Kuziel, S. Rivest, and T. Owens, “Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS,” Journal of Neuroscience, vol. 23, no. 21, pp. 7922–7930, 2003. View at Google Scholar · View at Scopus
  73. P. Majerova, M. Zilkova, Z. Kazmerova et al., “Microglia display modest phagocytic capacity for extracellular tau oligomers,” Journal of Neuroinflammation, vol. 11, no. 1, article 161, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Fricker, J. J. Neher, J.-W. Zhao, C. Théry, A. M. Tolkovsky, and G. C. Brown, “MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation,” The Journal of Neuroscience, vol. 32, no. 8, pp. 2657–2666, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. B. Spittau, J. Rilka, E. Steinfath, T. Zöller, and K. Krieglstein, “TGFβ1 increases microglia-mediated engulfment of apoptotic cells via upregulation of the milk fat globule-EGF factor 8,” GLIA, vol. 63, no. 1, pp. 142–153, 2015. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Komura, M. Miksa, R. Wu, S. M. Goyert, and P. Wang, “Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis via the lipopolysaccharide-CD14 pathway,” The Journal of Immunology, vol. 182, no. 1, pp. 581–587, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. Y. Liu, X. Yang, C. Guo, P. Nie, Y. Liu, and J. Ma, “Essential role of MFG-E8 for phagocytic properties of microglial cells,” PLoS ONE, vol. 8, no. 2, Article ID e55754, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Hanamsagar, V. Torres, and T. Kielian, “Inflammasome activation and IL-1β/IL-18 processing are influenced by distinct pathways in microglia,” Journal of Neurochemistry, vol. 119, no. 4, pp. 736–748, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. E.-J. Lee and H.-S. Kim, “Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells,” Neuroscience Letters, vol. 493, no. 1-2, pp. 38–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. Y. Bai, Z. Zhu, Z. Gao, and Y. Kong, “TLR2 signaling directs NO-dependent MMP-9 induction in mouse microglia,” Neuroscience Letters, vol. 571, pp. 5–10, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. K.-O. Cho, H. O. La, Y.-J. Cho, K.-W. Sung, and S. Y. Kim, “Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion,” Journal of Neuroscience Research, vol. 83, no. 2, pp. 285–291, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. C.-X. Wu, H. Sun, Q. Liu, H. Guo, and J.-P. Gong, “LPS induces HMGB1 relocation and release by activating the NF-κB-CBP signal transduction pathway in the murine macrophage-like cell line RAW264.7,” Journal of Surgical Research, vol. 175, no. 1, pp. 88–100, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. J. Guedes, A. L. C. Cardoso, and M. C. Pedroso de Lima, “Involvement of microRNA in microglia-mediated immune response,” Clinical and Developmental Immunology, vol. 2013, Article ID 186872, 11 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. C. S. Cãtaña, G. A. Calin, and I. Berindan-Neagoe, “Inflamma-miRs in aging and breast cancer: are they reliable players?” Frontiers in Medicine, vol. 2, article article 85, 2015. View at Publisher · View at Google Scholar
  85. S. R. Quinn and L. A. O'Neill, “A trio of microRNAs that control Toll-like receptor signalling,” International Immunology, vol. 23, no. 7, pp. 421–425, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. R. Saba, S. Gushue, R. L. C. H. Huzarewich et al., “MicroRNA 146a (miR-146a) is over-expressed during prion disease and modulates the innate immune response and the microglial activation state,” PLoS ONE, vol. 7, no. 2, Article ID e30832, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. K. D. Taganov, M. P. Boldin, K.-J. Chang, and D. Baltimore, “NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 33, pp. 12481–12486, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. M. A. Nahid, K. M. Pauley, M. Satoh, and E. K. L. Chan, “miR-146a is critical for endotoxin-induced tolerance: implication in innate immunity,” Journal of Biological Chemistry, vol. 284, no. 50, pp. 34590–34599, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. E. D. Ponomarev, T. Veremeyko, N. Barteneva, A. M. Krichevsky, and H. L. Weiner, “MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway,” Nature Medicine, vol. 17, no. 1, pp. 64–70, 2011. View at Publisher · View at Google Scholar · View at Scopus
  90. H. L. D. M. Willemen, X.-J. Huo, Q.-L. Mao-Ying, J. Zijlstra, C. J. Heijnen, and A. Kavelaars, “MicroRNA-124 as a novel treatment for persistent hyperalgesia,” Journal of Neuroinflammation, vol. 9, article 143, 2012. View at Publisher · View at Google Scholar · View at Scopus