EA 4427 SeRAIC-U.620 INSERM, Université de Rennes, Rennes, France.
J Cell Mol Med. 2010 Jun;14(6B):1726-39. doi: 10.1111/j.1582-4934.2009.00801.x. Epub 2009 Jun 5.
Interleukin-33 (IL-33), the most recently identified member of the IL-1 family, induces synthesis of T Helper 2 (Th2)-type cytokines via its heterodimeric ST2/IL-1RAcP receptor. Th2-type cytokines play an important role in fibrosis; thus, we investigated the role of IL-33 in liver fibrosis. IL-33, ST2 and IL-1RAcP gene expression was analysed in mouse and human normal (n= 6) and fibrotic livers (n= 28), and in human hepatocellular carcinoma (HCC; n= 22), using real-time PCR. IL-33 protein was detected in normal and fibrotic liver sections and in isolated liver cells using Western blotting and immunolocalization approaches. Our results showed that IL-33 and ST2 mRNA was overproduced in mouse and human fibrotic livers, but not in human HCC. IL-33 expression correlated with ST2 expression and also with collagen expression in fibrotic livers. The major sources of IL-33 in normal liver from both mice and human beings are the liver sinusoidal endothelial cells and, in fibrotic liver, the activated hepatic stellate cells (HSC). Moreover, IL-33 expression was increased in cultured HSC when stimulated by pro-inflammatory cytokines. In conclusion, IL-33 is strongly associated with fibrosis in chronic liver injury and activated HSC are a source of IL-33.
白细胞介素-33（IL-33）是 IL-1 家族中最新发现的成员，通过其异二聚体 ST2/IL-1RAcP 受体诱导 T 辅助 2（Th2）型细胞因子的合成。Th2 型细胞因子在纤维化中起着重要作用；因此，我们研究了 IL-33 在肝纤维化中的作用。使用实时 PCR 分析了小鼠和人类正常（n=6）和纤维化肝脏（n=28）以及人肝细胞癌（HCC；n=22）中的 IL-33、ST2 和 IL-1RAcP 基因表达。使用 Western blot 和免疫定位方法检测了正常和纤维化肝组织切片以及分离的肝细胞中的 IL-33 蛋白。我们的结果表明，IL-33 和 ST2 mRNA 在小鼠和人类纤维化肝脏中过度表达，但在人类 HCC 中没有。IL-33 表达与 ST2 表达以及纤维化肝脏中的胶原表达相关。来自小鼠和人类的正常肝脏中 IL-33 的主要来源是肝窦内皮细胞，而在纤维化肝脏中，主要来源是活化的肝星状细胞（HSC）。此外，当用促炎细胞因子刺激时，培养的 HSC 中 IL-33 的表达增加。总之，IL-33 与慢性肝损伤中的纤维化密切相关，活化的 HSC 是 IL-33 的来源。
