INTERFERON-GAMMA REGULATES COLLAGEN AND FIBRONECTIN GENE-EXPRESSION BY TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS

Interferon-gamma (IFN-gamma) regulates the expression of collagen and fibronectin genes by molecular mechanisms not completely understood, W e investigated the effects of IFN-gamma on the expression of the genes encoding alpha(1) (I) procollagen (COL1AI), alpha(1) (III) procollage n (COL3A1), and fibronectin (FN) in cultured normal human lung fibrobl asts. Labeled newly synthesized proteins were analysed by electrophore sis, mRNA levels and stability by Northern hybridizations, and transcr iption rates by in vitro assays. IFN-gamma caused a reduction in the p roduction of alpha(1)(I) and alpha(1)(III) procollagens and of fibrone ctin. The reduction in the production of procollagen chains was shown to result from a combination of IFN-gamma-induced inhibition of the tr anscription rates of the COL1AI and COL3A1 genes and destabilization o f the corresponding transcripts, IFN-gamma increased the transcription rate of FN, but also decreased the stability of the corresponding tra nscripts. The net results indicate that the regulation of the expressi on of extracellular matrix genes by IFN-gamma is a complex process tha t involves changes in gene transcription rates, alterations in mRNAs s tability, and possibly, modulation of the rates of translation. (C) 19 97 Elsevier Science Ltd. All rights reserved.