1. Osteopontin regulates interleukin-17 production in hepatitis
- Author
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Diao, Hongyan, Liu, Xiangdong, Wu, Zhongwen, Kang, Lei, Cui, Guangying, Morimoto, Junko, Denhardt, David T., Rittling, Susan, Iwakura, Yoichiro, Uede, Toshimitsu, and Li, Lanjuan
- Subjects
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OSTEOPONTIN , *GENE expression , *INTERLEUKIN-17 , *HEPATITIS , *CONCANAVALIN A , *IMMUNOGLOBULINS , *LABORATORY mice - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2012
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