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Cell Biology International (2010) 34, 287–292 (Printed in Great Britain)

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Regulation of protease-activated receptor-2 expression in gingival fibroblasts and Jurkat T cells by Porphyromonas gingivalis

Georgios N Belibasakis*†¹, Nagihan Bostanci* and Durga Reddi†

*Department of Oral Microbiology and General Immunology, Institute of Oral Biology, ZZMK, Faculty of Medicine, University of Zurich, Zurich, Switzerland, and †Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Periodontal disease destroys the tooth-supporting tissues as a result of chronic inflammation elicited by bacterial accumulation on tooth surfaces. Porphyromonas gingivalis is a major periodontal pathogen, with a significant capacity to perturb connective tissue homeostasis and immune responses in the periodontium, attributed to its virulence factors, including a group of secreted cysteine proteases (gingipains). PAR-2 (protease-activated receptor-2) is a G-protein-coupled receptor activated upon proteolytic cleavage, mediating intracellular signalling events related to infection and inflammation, such as cytokine production. GF (gingival fibroblasts) and T cells have central roles in periodontal inflammation, which can potentially be mediated by PAR-2. The aims of this study were to investigate the effects of P. gingivalis on PAR-2 gene expression in human GF and Jurkat T cells, using quantitative real-time PCR, and to evaluate the involvement of gingipains. After 6 h of challenge with ascending concentrations of P. gingivalis, PAR-2 expression was up-regulated in both cell types by approximately 5-fold, compared with the control. The P. gingivalis concentration required for maximal PAR-2 induction was 4-fold greater in GF than Jurkat T cells. Heat inactivation or chemical inhibition of cysteine proteases abolished the capacity of P. gingivalis to induce PAR-2 expression in Jurkat T cells. In conclusion, P. gingivalis can induce PAR-2 expression in GF and Jurkat T cells, potentially attributed to its gingipains. These findings denote that P. gingivalis may perturb the host immune and inflammatory responses by enhancing PAR-2 expression, thus contributing to the pathogenesis of periodontal disease.

Key words: gingipains, inflammation, protease-activated receptor-2 (PAR-2), Porphyromonas gingivalis, periodontal disease, signalling

Abbreviations: FBS, fetal bovine serum, GF, gingival fibroblasts, LPS, lipopolysaccharide, PAR-2, protease-activated receptor-2, TLCK, Na-p-tosyl-lysine chloromethyl ketone hydrochloride

¹To whom correspondence should be addressed (email george.belibasakis@zzmk.uzh.ch).

Received 9 October 2009/4 November 2009; accepted 6 November 2009

Published as Cell Biology International Immediate Publication 6 November 2009, doi:10.1042/CBI20090290

© 2010 The Author(s) Journal compilation © 2010 Portland Press Ltd