Published online Mar 28, 2006. doi: 10.3748/wjg.v12.i12.1918
Revised: July 20, 2005
Accepted: July 25, 2005
Published online: March 28, 2006
AIM: To study the effects of interleukin-10 (IL-10) on the expression of α-smooth muscle actin (α-SMA), nuclear factor-κB(NF-κB) and Fas/Fas ligand (FasL) in hepatic stellate cells of experimental rats with hepatic fibrosis.
METHODS: Sixty clean SD rats were randomly divided into control group (group N), liver fibrotic group (group C) and IL-10 treatment group (group I). Control group received intraperitoneal injection of saline (2ml•kg-1), twice a week. Fibrotic group was injected intraperitoneally with 50% carbon tetrachloride (CCl4) (2 ml•kg-1), twice a week. IL-10 treatment group was given IL-10 at a dose of 4 µg•kg-1 20 minutes before CCl4 administration from the third week. Hepatic stellate cells (HSCs) were isolated from these rats at the seventh and eleventh weeks during the course of liver fibrosis, respectively. The expression of α-SMA and NF-κB in HSCs was measured by S-P immunohistochemistry. The expression of Fas and FasL mRNA was measured by RT-PCR. Furthermore, liver tissues were harvested from three groups at the same time.
RESULTS: The CCl4- induced experimental rat hepatic fibrosis model was established successfully. The purity of extracted hepatic stellate cells was about 95% and the yield of hepatic stellate cells was 1.2-2.3×106/g liver tissue averagely. The positive expression of α-SMA and NF-κB was 36.5% and 28.5% respectively in group N. The positive levels of α-SMA and NF-κB were increased significantly in group C compared to group N (P<0.01). The positive signals decreased significantly (P<0.05) in group I. In the 11th week, the HSCs of group I became round with visible pyknotic nuclei. The expression of NF-κB in group C was significantly increased in a time-dependentmanner (P<0.01), but there was no difference in the α-SMA expression (P >0.05). The mRNA of Fas and FasL in group C was significantly increased in a time-dependent manner compared to that in control group. After treated with IL-10, the expression level of Fas and FasL was higher in group I than in group C.
CONCLUSION: The positive expression of α-SMA and NF-κB in hepatic stellate cells is decreased by ectogenic IL-10 in liver fibrosis induced by CCl4. The expression of Fas and FasL is increased in the course of liver fibrosis, and is further increased by IL-10. IL-10 could inhibit the activation of HSCs and cause apoptosis of activated HSCs.