Regulation of type I plasminogen activator inhibitor in human gingival fibroblasts with cyclosporine A

Oral Diseases (2010) 16 , 396–401 Objectives: Cyclosporine A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of gingival overgrowth. Type I plasminogen activator inhibitor (PAI‐1) has shown to play an important role in CsA‐induced gingival overgrowth. However, little is known about whether factors can modulate CsA‐induced PAI‐1 expression. Methods: Cytotoxicity, reverse transcriptase‐polymerase chain reaction, and enzyme‐linked immunosorbent assay were used to investigate the effects of Human gingival fibroblasts (HGFs) exposed to CsA. In addition, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, interlukin‐1α, tumor necrosis factor‐α, mitogen‐activated protein kinase kinase (MEK) inhibitor U0126, signal‐regulated protein kinase (ERK) inhibitor PD98059 and cell‐permeable glutathione precursor N‐acetyl‐L‐cysteine (NAC) were added to test how they modulated the effects of CsA‐induced PAI‐1 expression. Results: The concentration of CsA higher than 500 ng ml^?1 demonstrated cytotoxicity to HGFs (P < 0.05). Periodontal pathogens as well as proinflammatory cytokines were found to increase the CsA‐induced PAI‐1 mRNA and protein expression (P < 0.05). Pharmacological agents NAC, U0126, and PD98059 were found to decrease the CsA‐induced PAI‐1 mRNA and protein expression (P < 0.05). Conclusions: Cyclosporine A (CsA) may predispose to gingival overgrowth under inflammatory environments. The regulation of PAI‐1 expression induced by CsA might be critically related with the intracellular glutathione and the ERK‐MAPK pathway.