期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 14, 期 6B, 页码 1726-1739出版社
WILEY
DOI: 10.1111/j.1582-4934.2009.00801.x
关键词
IL-33; ST2; fibrosis; hepatic stellate cells; Th2 cytokines
资金
- ministere de la recherche et de l'enseignement superieur
- INSERM
- ligue nationale contre le cancer
- region Bretagne
- agence nationale de recherche sur le SIDA
- societe nationale francaise de gastroenterologie
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.
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