期刊
CYTOKINE
卷 60, 期 1, 页码 129-137出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2012.06.287
关键词
Osteopontin; IL-17; Chronic hepatitis B; Concanavalin A-induced hepatitis
资金
- New Century Excellent Talents [NCET-09-0686]
- Science and Technology Department Foundation of Zhejiang Province [2010R10061]
- Fundamental Research Funds for the Central Universities [2009QNA7033]
- Grants-in-Aid for Scientific Research [21390113] Funding Source: KAKEN
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. 03 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-kappa B 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. (C) 2012 Elsevier Ltd. All rights reserved.
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