N. Sugano et al., Cyclosporin A inhibits collagenase gene expression via AP-1 and JNK suppression in human gingival fibroblasts, J PERIOD RE, 33(8), 1998, pp. 448-452
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.