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

Abstract:

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-1alpha, tumor necrosis factor-alpha, 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.

journal_name

Oral Dis

journal_title

Oral diseases

authors

Ho YC,Lin HJ,Tsai CH,Chang YC

doi

10.1111/j.1601-0825.2009.01653.x

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

396-401

issue

4

eissn

1354-523X

issn

1601-0825

pii

ODI1653

journal_volume

16

pub_type

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