1887

Abstract

The interaction between epithelial cells and micro-organisms is often a crucial initiating event in infectious diseases. Infection with , a Gram-negative anaerobe, is strongly associated with severe periodontal disease. This bacterium possesses an array of virulence factors, some of which can induce apoptosis. The tumour necrosis factor (TNF) receptor family is involved in the regulation of cellular homeostasis, cell surface molecules involved in phagocytosis, Fas ligand (L) expression and activation of the caspase cascade resulting in DNA fragmentation and cell blebbing. The current study examined the role of nuclear factor-B (NFB) in FasL-mediated apoptotic cell death in primary human gingival epithelial cells (HGEC) induced by heat-killed , probably through TLR signalling pathways. A marked up-regulation of TLR2 and Fas–FasL was detected in HGEC stimulated with . Activation of NFB by in HGEC was demonstrated by an NFB promoter luciferase assay as well as by phosphorylation of p65 as detected by Western blotting. Activation of cleaved caspase-3 and caspase-8 resulted in apoptotic cell death of HGEC. The survival proteins c-IAP-1/c-IAP-2 were decreased in HGEC exposed to . HGEC apoptosis induced by was inhibited by an anti-human FasL monoclonal antibody. Blockade of NFB by helenalin resulted in down-regulation of FasL whereas a caspase-8 inhibitor did not decrease FasL. Taken together, these studies show that can induce epithelial cell apoptosis through Fas–FasL up-regulation and activation of caspase-3 and caspase-8.

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2006-03-01
2020-04-01
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