Interleukin-1beta 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-1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation. METHODS: IL-1beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs production. RESULTS: IL-1beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/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-1beta-induced MMPs production. On the contrary, IL-1beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta 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-1beta is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and contribute to the loss of interstitial collagen in skin photoaging.