Selective inhibition of human diploid fibroblast collagen synthesis by interferons.
The effects of alpha- and gamma-interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified alpha-IFNs and affinity purified gamma-IFNs caused greater than 50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant alpha-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified alpha-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that alpha- and gamma-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.
D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000302:isolation & purification; D012867:Skin / Q000378:metabolism
D002250:Carbon Radioisotopes; D007370:Interferon Type I; D011506:Proteins; D007371:Interferon-gamma; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline