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Areca nut extract‐treated gingival fibroblasts modulate the invasiveness of polymorphonuclear leukocytes via the production of MMP‐2
Author(s) -
Lu HsuanHsuan,
Chen LiKai,
Cheng ChiehYuan,
Hung ShanLing,
Lin ShuChun,
Chang KuoWei
Publication year - 2009
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2008.00717.x
Subject(s) - areca , pathogenesis , fibroblast , matrix metalloproteinase , interleukin 8 , senescence , zymography , blot , oral submucous fibrosis , immunology , inflammation , cell , gingivitis , pathology , medicine , biology , in vitro , microbiology and biotechnology , biochemistry , dentistry , nut , gene , engineering , structural engineering
Background: Areca nut chewing is associated with an increase in the incidence of oral neoplastic or inflammatory diseases. Aberrations in matrix metalloprotease (MMP) expression are associated with the pathogenesis of oral diseases. This study investigated the potential effects of areca nut extract (ANE) on human gingival fibroblasts and the consequential impacts on inflammatory pathogenesis. Methods: Analyses of senescence marker, cell viability, changes of the cell cycle, and cell granularity in gingival fibroblasts together with an assessment of the invasiveness of polymorphonuclear (PMN) leukocytes after treatment with the supernatant of ANE‐treated gingival fibroblasts were performed to characterize the phenotypic impacts. Western blotting and gelatin zymography were used to assay the expression and activity of MMP‐2. Results: Chronic subtoxic (<10 μg/ml) ANE treatment resulted in premature growth arrest, appearance of senescence‐associated β‐galactosidase activity and various other senescence‐associated phenotypes in gingival fibroblasts. Gingival fibroblasts established from older individuals had a higher propensity to become ANE‐induced senescent gingival fibroblasts. An activation of MMP‐2 was identified in senescent cells. PMN leukocytes treated with the supernatant of ANE‐induced senescent cells exhibited a significant increase in invasiveness, which was abrogated by both a MMP‐2 blocker and a MMP‐2 nullifying antibody. Conclusions: This study provides evidence whereby MMP‐2 secreted from ANE‐induced senescent gingival fibroblasts would facilitate the invasiveness of PMN leukocytes, which could be associated with the oral inflammatory process in areca chewers.