Differential regulation of glycosaminoglycan, fibronectin, and collagenase production in cultured human dermal fibroblasts by interferon-alpha, -beta, and -gamma

Abstract

In order to determine whether interferons (IFNs) play a universal role in terminating the fibrotic response by inhibiting other fibroblast functions in addition to growth and collagen production, we investigated the effect of human recombinant (hu-r) IFN-alpha, -beta, and -gamma on the glycosaminoglycan, fibronectin, and collagenase production of cultured human dermal fibroblasts. Our results show that short-term (48 h) treatment of confluent fibroblast cultures with hu-r-IFN-alpha 2 and hu-r-IFN-beta-ser17 causes a concentration (1 to 1 x 10(5) U/ml)-dependent inhibition of glycosaminoglycan production, has no effect on fibronectin production, and markedly increases collagenase production. In contrast, hu-r-IFN-gamma not only causes a concentration-dependent increase in collagenase production but also increases both glycosaminoglycan and fibronectin production. These results demonstrate that IFNs differently regulate fibroblast functions rather than universally inhibit all functions, and show that IFN-alpha and -beta exhibit a broader antifibrotic spectrum that IFN-gamma.