Interleukin-1 beta and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression

Background: Exposure to solar UV radiation is the main environmental factor that causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member of the MMP family and degrades types I and III collagens, which are the major structural components of the dermis. Objective: We evaluated the involvement IL-1 beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation. Methods: IL-1 beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1 alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1 beta-induced MMPs production. Results: IL-1 beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1 beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1 alpha/beta-deficient mice produced significantly decreased levels of MMPs compared to wild-type mice after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much Less sensitive to IL-1 beta-induced MMPs production. On the contrary, IL-1 beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1 beta stimulation was found to be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK inhibitor and inhibitor were found to have little effect on expression of MMP-1 mRNA. Conclusions: IL-1 beta is involved in the up-reguiation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1 beta and MIF cytokine network induce MMP-1 and contribute to the toss of interstitial collagen in skin photoaging. (C) 2007 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.