Differential effects of gamma-interferon on collagen and fibronectin gene expression.
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.
D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics*; D005796:Genes / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D005353:Fibronectins; D007371:Interferon-gamma; D003094:Collagen; D004247:DNA