Cordycepin inhibits IL-1β- induced MMP-1 and MMP-3 expression in synovial fibroblasts

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Matrix metalloproteinase (MMP) is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in tumor invasion and metastasis. Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom, is reported to possess many pharmacological activities including, anti-cancer, anti-inflammatory and anti-infection activities. In this study, we examined the inhibitory effect of cordycepin on IL-1β-induced MMP-1 and MMP-3 expression in synovial fibroblasts. Cordycepin significantly inhibited IL-1β-induced MMP-1 and MMP-3 expression in synovial fibroblasts. Therefore, we performed the study to identify what signaling pathways are involved in IL-1β-induced MMP-1 and MMP-3 expression in synovial fibroblasts. Among various signaling modifiers, SB203580, p38 MAP kinase inhibitor strongly induced a marked reduction in MMP-1 and MMP-3 expression, indicating that p38 MAPK signaling cascade could play an important role in IL-1β-induced MMP-1 and MMP-3 expression. As we expected, cordycepin significantly inhibited IL-1β -induced p38 MAPK activation. Taken together, our results suggest that cordycepin inhibited IL-1β-induced MMP-1 and MMP-3 expression in synovial fibroblasts. In conclusion, cordycepin may provide a potential therapeutic approach for cytokine/MMP-associated disorders such as cancer and chronic inflammation.