Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression.
In this study, we assessed the hypothesis that angiotensin (Ang) II could modulate inflammatory cell recruitment into the liver through hepatic expression of monocyte chemoattractant protein (MCP)-1 during liver injury. For in vivo study, Ang II type la knockout (ATla KO) mice and wild-type (WT) mice were treated with CCl4 for 4 weeks. After CCl4 treatment, ATla KO mice showed lower expression of MCP-1 and fewer CD68-positive cells in the liver compared with WT mice. For in vitro study, Ang II was added to LI90 cells. Ang II enhanced MCP-1 mRNA together with RhoA mRNA and also induced secretion of MCP-1 into the culture medium. This change was strongly blocked by Y-27632, a specific Rho-kinase inhibitor. These results suggest that Ang II modulates hepatic inflammation via production of MCP-1 by hepatic stellate cells, and the effect of Ang II on MCP-1 production is, at least partly, mediated by the Rho/Rho-kinase pathway.
Kanno
Keishi
K
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Tazuma
Susumu
S
Nishioka
Tomoji
T
Hyogo
Hideyuki
H
Chayama
Kazuaki
K
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D006505:Hepatitis / Q000378:metabolism*; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008103:Liver Cirrhosis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D054460:rho-Associated Kinases
D015703:Antigens, CD; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases