Interferon-γ inhibits the myofibroblastic phenotype of rat palatal fibroblasts induced by transforming growth factor-β1 in vitro

Interferon-gamma (IFN-gamma), a multifunctional cytokine, has been noted as a potential therapeutic agent for various fibrotic disorders, including excessive scar tissue formation, We previously reported that transforming growth factor-beta 1 (TGF-beta 1) induced the myofibroblastic phenotype in palatal fibroblasts derived from palatal mucosa, and that such effects might have a close link to palatal scar formation. In the present study, we examined the effects of IFN-gamma on TGF-beta 1-pretreated palatal fibroblasts for the purpose of clarifying the suppressive potency against myofibroblastic phenotype expression in vitro. IFN-gamma significantly altered the spindle morphology of TGF-beta 1-pretreated palatal fibroblasts into the polygonal one that was similar to the non-treated palatal fibroblasts, This change was parallel with a decrease in the expression of alpha-smooth muscle actin protein, a marker for myofibroblast, as determined by immunoblot analysis. Northern blot analysis showed that IFN-gamma inhibited pro alpha 2(I) collagen mRNA expression that was stimulated by TGF-beta 1 pretreatment for 24 h, Furthermore, IFN-gamma decreased the cell contractility enhanced by TGF-beta 1 pretreatment for 24 h in a three-dimensional collagen gel culture system. These results suggest that IFN-gamma may have negative effects with regard to controlling the myofibroblastic phenotype induced by TGF-beta 1 in palatal fibroblasts, (C) 1999 Federation of European Biochemical Societies.