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 overgrowth. Although the molecular mechanisms of CsA-induced gingival overgrowth are still unknown, it has been postulated that CsA acts on lipopolysaccharide (LPS) to induce fibroblastic activity, which results in an increase of the extracellular matrix. Here we provide evidence that CsA is able to affect signal transduction of LPS-induced collagenase expression in fibroblasts. Treatment of fibroblasts with LPS caused activation of collagenase gene, activator protein-1 (AP-1) and c-Jun N-terminal kinase (JNK). These activations were blocked by CsA. We suggest that inhibitory effects of CsA on LPS-induced signal transduction may contribute to the mechanism of CsA-induced gingival overgrowth.
Sugano
N
N
Nihon University School of Dentistry, Department of Periodontology, Tokyo, Japan. sugano-n@dent.nihon-u.ac.jp
Ito
K
K
Murai
S
S
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000201:enzymology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases; D011480:Protease Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D018808:Transcription Factor AP-1; D016572:Cyclosporine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D017364:Collagenases