Cyclosporin A inhibits collagenase gene expression via AP-1 and JNK suppression in human gingival fibroblasts

A frequent side effect of cyclosporin A (CsA) administration is gingival ov ergrowth. Although the molecular mechanisms of CsA-induced gingival overgro wth are still unknown, it has been postulated that CsA acts on lipopolysacc haride (LPS) to induce fibroblastic activity, which results in an increase of the extracellular matrix. Here we provide evidence that CsA is able to a ffect signal transduction of LPS-induced collagenase expression in fibrobla sts. Treatment of fibroblasts with LPS caused activation of collagenase gen e, activator protein-1 (AP-1) and c-Jun N-terminal kinase (JNK). These acti vations were blocked by CsA. We suggest that inhibitory effects of CsA on L PS-induced signal transduction may contribute to the mechanism of CsA-induc ed gingival overgrowth.