Osteopontin regulates interleukin-17 production in hepatitis
Osteopontin regulates interleukin-17 production in hepatitis
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DOI：
10.1016/j.cyto.2012.06.287
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发表时间：
2012-10-01
期刊：
影响因子：
3.8
通讯作者：
Li, Lanjuan
中科院分区：
文献类型：
--
作者：
Diao, Hongyan;Liu, Xiangdong;Li, Lanjuan
骨桥蛋白的过度表达与多种炎症性肝病有关。有趣的是，这些疾病中的每一种也与IL-17表达相关。因此，我们试图确定骨桥蛋白和IL-17之间是否存在任何机制联系。在此，我们发现IL-17和骨桥蛋白水平在慢性B型肝炎患者中显著升高。我们发现，IL-17和骨桥蛋白水平增加相似，在小鼠伴刀豆球蛋白A诱导的肝炎。骨桥蛋白和IL-17缺陷小鼠对刀豆球蛋白A诱导的肝损伤具有抗性。此外，骨桥蛋白显着诱导白细胞（从人类和小鼠）的IL-17的表达。这种作用可被骨桥蛋白的特异性抗体阻断。03整合素（骨桥蛋白受体之一）在骨桥蛋白诱导IL-17产生中起关键作用。骨桥蛋白诱导的IL-17表达通过p38介导。JNK和NF-κ B途径。这些发现表明，骨桥蛋白调节IL-17的生产过程中的肝炎发病机制，并提供了新的证据，骨桥蛋白和IL-17在肝炎中的关键作用。(C)2012爱思唯尔有限公司保留所有权利。
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.