Inducible IL-23p19 expression in human microglia via p38 MAPK and NF-kappaB signal pathways.
Activated microglia can release a variety of proinflammatory cytokines that play a crucial role in the pathogenesis of multiple sclerosis (MS). IL-23, a novel proinflammatory cytokine, is required for the induction of experimental autoimmune encephalomyelitis. Previously we demonstrated that IL-23 is expressed in MS lesions and that microglia are one cellular source of IL-23 in MS patients. In the present study we investigated the inducible expression and regulation of p19, a key subunit of IL-23, in human microglia. We demonstrated the inducible expression of IL-23p19 by lipopolysaccharide-stimulated microglial cells. Using signaling pathway-specific inhibitors, we showed that blocking p38 MAP kinase or NF-kappaB signaling pathway significantly reduced p19 expression in microglia. The regulatory role of p38 MAP kinase in p19 expression was further confirmed by decreased expression in microglia transduced with dominant-negative p38. We concluded that the p38 MAP kinase and NF-kappaB signaling pathways play an important role in regulation of IL-23p19 expression on human microglia, and are thus potential therapeutic targets in the treatment of MS.
Li
Yonghai
Y
Department of Neurology, Thomas Jefferson University, 300 JHN Building, 900 Walnut Street, Philadelphia, PA 19107, USA.
Chu
Niansheng
N
Hu
Aihua
A
Gran
Bruno
B
Rostami
Abdolmohamad
A
Zhang
Guang-Xian
GX
D002460:Cell Line; D048430:Cell Shape; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D009103:Multiple Sclerosis / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D053760:Interleukin-23 Subunit p19; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases