Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis.
OBJECTIVE
To study the effects of interleukin-10 on hepatic stellate cells and liver tissue in experimental rats hepatic fibrosis.


METHODS
Rat hepatic fibrosis model induced by carbon tetrachloride was established. Liver tissues were harvested from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. The expression of TGF-beta1, MMP-2 and TIMP-1 in the liver tissues was measured by S-P immunohistochemistry. In addition, another model was established; HSCs in rats in each group were isolated. RT-PCR was employed to analyze TGF-beta1, MMP-2 and TIMP-1 mRNA expression in cells and immunocytochemistry was performed to detect protein expression of alpha-SMA, NF-kappaB, TGF-beta1, MMP-2 and TIMP-1 in HSCs.


RESULTS
Rat hepatic fibrosis was developed successfully. The fibrosis changes were partially reversed by simultaneous administration of IL-10. The positive signals of TGF-beta1, MMP-2 and TIMP-1 were observed more frequently (P<0.05) in the CCl4-treated group compared to those in the IL-10-treated group and the control group. HSCs were successfully isolated. TGF-beta1, MMP-2 and TIMP-1 mRNA in HSCs increased obviously during the course of hepatic fibrosis, and their levels were decreased after the treatment with IL-10 (P<0.05). The immunocytochemistry positive levels for TGF-beta1, MMP-2, TIMP-1, alpha-SMA and NF-kappaB in the fibrogenesis group were increased significantly compared to the normal group (P<0.01). The positive signals decreased significantly (P<0.05) after the treatment with IL-10.


CONCLUSIONS
The expression of TGF-beta1, MMP-2 and TIMP-1 increased in liver or in HSC of hepatic fibrosis rats and decreased after treatment with IL-10. The IL-10 could inhibit the activation of HSCs and make an antifibrogenic process come into effect in this way.
Zhang
Li-Juan
LJ
Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China.
Zheng
Wei-Da
WD
Chen
Yun-Xin
YX
Huang
Yue-Hong
YH
Chen
Zhi-Xin
ZX
Zhang
Sheng-Jun
SJ
Shi
Mei-Na
MN
Wang
Xiao-Zhong
XZ
D000199:Actins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004586:Electrophoresis; D005342:Fibrinolysis / Q000502:physiology*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000502:physiology*; D008099:Liver / Q000166:cytology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D016328:NF-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D020778:Matrix Metalloproteinase 2