Differential effects of gamma-interferon on collagen and fibronectin gene expression.

Abstract

The interferons are a group of endogenous proteins that exhibit a variety of biological functions in addition to their ability to induce resistance to viruses. In order to evaluate the anti-fibrogenic actions of interferon, we have delineated the level of regulation responsible for gamma-interferon-induced changes in collagen and fibronectin gene expression in cultured fibroblasts. Confluent human skin fibroblasts were exposed to 500 anti-viral units/ml of gamma-interferon. RNA was then extracted from the cells, and steady-state mRNA levels were determined by Northern and dot blot hybridization studies. Cells exposed to interferon had type I procollagen mRNA levels that were 23% of control and type III procollagen mRNA levels only 7% of control. The interferon-treated cells also had beta-actin mRNA levels that were decreased to 51% that of untreated cells but had fibronectin steady-state mRNA levels that were 560% of control levels. Nuclear run-on assays revealed that interferon did not affect the transcriptional rates of types I and III collagen or beta-actin, but it did increase the transcriptional rate of fibronectin to 670% of control levels. These findings demonstrate that gamma-interferon causes a marked decrease in types I and III procollagen mRNA levels in vitro by a post-transcriptional mechanism while inducing fibronectin expression at a transcriptional level.