title: Osteopontin regulates interleukin-17 production in hepatitis.
abstract: The overexpression of osteopontin is associated with various inflammatory liver diseases. Interestingly, each of these diseases is also associated with IL-17 expression. Therefore, we sought to determine whether there is any mechanistic link between osteopontin and IL-17. Herein we show that IL-17 and osteopontin levels were significantly increased in patients with chronic hepatitis B. We found that IL-17 and osteopontin levels increased similarly in mice with concanavalin A-induced hepatitis. Both osteopontin- and IL-17-deficient mice were resistant to concanavalin A-induced hepatic injury. In addition, osteopontin markedly induced IL-17 expression by leukocytes (from humans and mice). This effect could be blocked by a specific antibody against osteopontin. β3 integrin (one of the osteopontin receptors) was critically involved in the induction of IL-17 production by osteopontin. Osteopontin-induced IL-17 expression was mediated through the p38, JNK, and NF-κB pathways. These findings suggest that osteopontin regulates IL-17 production during the pathogenesis of hepatitis and provide new evidence for the critical roles of osteopontin and IL-17 in hepatitis.
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors: Hongyan
authors: H
authors: Diao
authors: Xiangdong
authors: X
authors: Liu
authors: Zhongwen
authors: Z
authors: Wu
authors: Lei
authors: L
authors: Kang
authors: Guangying
authors: G
authors: Cui
authors: Junko
authors: J
authors: Morimoto
authors: David T
authors: DT
authors: Denhardt
authors: Susan
authors: S
authors: Rittling
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Toshimitsu
authors: T
authors: Uede
authors: Lanjuan
authors: L
authors: Li
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics; D003208:Concanavalin A / Q000633:toxicity; D004351:Drug Resistance / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D053495:Osteopontin / Q000097:blood* / Q000235:genetics; D010455:Peptides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D020381:Interleukin-17; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D053495:Osteopontin; D003208:Concanavalin A; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases