YU-CHAO CHANG2026-10-162026-10-162010-05-01Pure ID: 15121295Pure UUID: 2096646a-1bb9-404c-96a5-9fd5820ead1610.1111/j.1601-0825.2009.01653.xhttps://www.scopus.com/pages/publications/77950504880https://scholars.csmu.edu.tw/handle/123456789/27775Oral 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.6enjournal article