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 matrix metalloproteinase-1 (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, basal and UVinduced 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 dose-dependently increased by C 2 -ceramide or SMase treatment. The activation of ceramide pathway by C 2 -ceramide enhanced phosphorylation of signal transducer and activators of transcription-1 (STAT-1), whereas ceramide-induced MMP-1 expression was potently prevented by piceatannol; Janus kinase ( 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 UV-induced 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. UV (UV) irradiation is a major cause of epidermal inflammation, immunosuppression, altered epidermal permeability barrier function, premature aging, dyspigmentation, and the development of nonmelanoma and melanoma skin cancers (1-4). In addition, UV significantly increases the amount of intracellular ceramide, which is a major component of skin lipid and a lipid second messenger (5, 6). In addition, UV-damaged skin was more resistant to damage than normal skin, indicating improvement of the barrier function through induction of the amount of all stratum corneum lipids (7). These effects may be related to an increase in the stratum corneum ceramides (8). Activation of SMase by UV may be rapidly generated ceramide from hydrolysis of sphingomyelin at the plasma membrane (9).Ceramide has a number of important physiological functions that regulate cellular homeostasis, such as cell proliferation, differentiation, and apoptosis (10-13). As an intermediate in sphingomyelin biosynthesis, ceramide plays a key role in the metabolism of molecules that comprise membranes (14, 15). In addition, membrane ceramides contribute to membrane structure by influencing membrane lipid ordering by affecting membrane porosity and by altering the permeability of cell membranes (15, 16). Ceramide activates downstream targets including ceramide activated protein kinase, stress-activated protein kinase/c-Jun N-terminal kinase ( JNK), protein kinase C, ceramide activated phosphatase,...