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

Abstract

Interferon-γ (IFN-γ), 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-β1 (TGF-β1) 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-γ on TGF-β1-pretreated palatal fibroblasts for the purpose of clarifying the suppressive potency against myofibroblastic phenotype expression in vitro. IFN-γ significantly altered the spindle morphology of TGF-β1-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 α-smooth muscle actin protein, a marker for myofibroblast, as determined by immunoblot analysis. Northern blot analysis showed that IFN-γ inhibited proα2(I) collagen mRNA expression that was stimulated by TGF-β1 pretreatment for 24 h. Furthermore, IFN-γ decreased the cell contractility enhanced by TGF-β1 pretreatment for 24 h in a three-dimensional collagen gel culture system. These results suggest that IFN-γ may have negative effects with regard to controlling the myofibroblastic phenotype induced by TGF-β1 in palatal fibroblasts