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.