Regulation of protease-activated receptor-2 expression in gingival fibroblasts and Jurkat T cells by Porphyromonas gingivalis.
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.
Belibasakis
Georgios N
GN
Department of Oral Microbiology and General Immunology, Institute of Oral Biology, ZZMK, Faculty of Medicine, University of Zurich, Zurich, Switzerland. george.belibasakis@zzmk.uzh.ch
Bostanci
Nagihan
N
Reddi
Durga
D
D002460:Cell Line; D057056:Cysteine Proteases / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000382:microbiology; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D019169:Jurkat Cells; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D015854:Up-Regulation
D044464:Receptor, PAR-2; D057056:Cysteine Proteases