Ceramide accelerates ultraviolet (UV)-induced MMP-1 expression through JAK1/STAT-1 pathway in cultured human dermal fibroblasts

Ultraviolet (UV) irradiation accelerates formation of ceramide through hydrolysis of sphingomyelin and de novo synthesis. Here, we investigated the effects of ceramide on UV-induced MMP-1 expression in human dermal fibroblasts. Our results showed that acidic-sphingomyelinase (aSMase) and MMP-1 mRNA expression were increased by UV irradiation. Treatment of D609 (aSMase inhibitor) decreased the level of basal and UVinduced MMP-1 expression. On the other hand, both basal and UV-induced MMP-1 expression was increased through induction of intracellular ceramide by D-MAPP, a ceramidase inhibitor. Our results also showed that MMP-1 protein expression was dosedependently increased by C 2 -ceramide or SMase treatment. The activation of ceramide pathway by C 2 -ceramide enhanced phosphorylation of STAT-1, whereas ceramide-induced MMP-1 expression was potently prevented by piceatannol, JAK1 inhibtor, and WHI-P131, a specific inhibitor of JAK3, but not by AG490, JAK 2 inhbitor, in human dermal fibroblasts. We also found that UV induced the phosphorylation of STAT-1 and UVinduced MMP-1 expression was significantly decreased by JAK1 inhibitor, piceatannol. Overall, we demonstrate that induction of intracellular ceramide by UV may activate MMP-1 gene expression via JAK1/STAT-1 pathway. Therefore, we suggest that targeted modulation of the ceramide signaling pathway may offer a novel therapeutic approach for inhibiting MMP-1 expression which is a causing gene of skin aging.