Interleukin-33 overexpression is associated with liver fibrosis in mice and humans.
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.
Marvie
Pierrick
P
EA 4427 SeRAIC-U.620 INSERM, Université de Rennes, Rennes, France.
Lisbonne
Mariette
M
L'helgoualc'h
Annie
A
Rauch
Michel
M
Turlin
Bruno
B
Preisser
Laurence
L
Bourd-Boittin
Katia
K
Théret
Nathalie
N
Gascan
Hugues
H
Piquet-Pellorce
Claire
C
Samson
Michel
M
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C506536:IL33 protein, human; C506535:Il33 protein, mouse; D053577:Interleukin-1 Receptor Accessory Protein; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger