Objective: To observe the effects of interferon-alpha on the proliferation and mRNA expression of procollagen type I and III and on the deposition of collagen type I and III in fibrotic liver of rats.
Methods: CCl4 was used to induce the liver fibrosis rat model. The stellate cells were isolated from liver and cultured in DMEM medium. The effects of interferon-alpha on the proliferation and collagen synthesis of stellate cells were determined with 3H-TdR, 3H-proline incorporating test. Total RNA of stellate cells was extracted and the cDNA of procollagen type I and III and of interstitial collagenase was labeled using Dig High Primer technique. The level of procollagen type I and III and interstitial collagenase mRNA were measured by Northern blot analysis. Deposition of collagen type I and III in fibrotic liver was evaluated with Dot blot.
Results: At the 4th, 24th and 48th hour, interferon-alpha inhibited the intake of 3H-TdR and 3H-proline by stellate cells significantly. The inhibition rates were 16%, 19% and 27%, respectively. The intensity of inhibition was proportional to the concentration of interferon-alpha. The expression level of procollagen type I and III mRNA in the interferon-alpha treated group was significantly lower than that in control group in all stages of fibrosis. At the 2nd and 6th week, the deposition of collagen type I and III in interferon-alpha treated group decreased significantly compared with that in control group. However, no difference was found at the 9th week. The expression of collagenase mRNA between interferon-alpha treated group and control group showed no difference.
Conclusion: Interferon-alpha can inhibid the proliferation and collagen synthesis of stellate cells, down-regulate the expressions of procollagen type I and III mRNA and reduce the deposition of collagen type I and III in fibrotic liver. It has no effect on collagenase.