Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion

Periodontitis is a chronic inflammatory disease affecting oral tissues. Oral epithelial cells represent the primary barrier against bacteria causing the disease. We examined the responses of such cells to an arginine-specific cysteine proteinase (RgpB) produced by a causative agent of periodontal di...

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Bibliographic Details
Published in:	Infection and immunity 2001-08, Vol.69 (8), p.5121-5130
Main Authors:	LOURBAKOS, Afrodite, POTEMPA, Jan, TRAVIS, James, DANDREA, Michael R, ANDRADE-GORDON, Patricia, SANTULLI, Rosemary, MACKIE, Eleanor J, PIKE, Robert N
Format:	Article
Language:	eng
Subjects:	Adhesins, Bacterial Animals Bacteriology Biological and medical sciences Calcium - metabolism Cell Line CHO Cells Cricetinae Cysteine Endopeptidases - metabolism Endopeptidases - metabolism Epithelial Cells - cytology Epithelial Cells - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Genetics Gingiva - cytology Gingiva - metabolism Hemagglutinins - metabolism Host Response and Inflammation Humans Interleukin-6 - metabolism Microbiology Mouth Mucosa - cytology Mouth Mucosa - metabolism Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Porphyromonas gingivalis Porphyromonas gingivalis - enzymology Receptor, PAR-1 Receptor, PAR-2 Receptors, Thrombin - genetics Receptors, Thrombin - metabolism
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Summary:	Periodontitis is a chronic inflammatory disease affecting oral tissues. Oral epithelial cells represent the primary barrier against bacteria causing the disease. We examined the responses of such cells to an arginine-specific cysteine proteinase (RgpB) produced by a causative agent of periodontal disease, Porphyromonas gingivalis. This protease caused an intracellular calcium transient in an oral epithelial cell line (KB), which was dependent on its enzymatic activity. Since protease-activated receptors (PARs) might mediate such signaling, reverse transcription-PCR was used to characterize the range of these receptors expressed in the KB cells. The cells were found to express PAR-1, PAR-2, and PAR-3, but not PAR-4. In immunohistochemical studies, human gingival epithelial cells were found to express PAR-1, PAR-2, and PAR-3 on their surface, but not PAR-4, indicating that the cell line was an effective model for the in vivo situation. PAR-1 and PAR-2 expression was confirmed in intracellular calcium mobilization assays by treatment of the cells with the relevant receptor agonist peptides. Desensitization experiments strongly indicated that signaling of the effects of RgpB was occurring through PAR-1 and PAR-2. Studies with cells individually transfected with each of these two receptors confirmed that they were both activated by RgpB. Finally, it was shown that, in the oral epithelial cell line, PAR activation by the bacterial protease-stimulated secretion of interleukin-6. This induction of a powerful proinflammatory cytokine suggests a mechanism whereby cysteine proteases from P. gingivalis might mediate inflammatory events associated with periodontal disease on first contact with a primary barrier of cells.
ISSN:	0019-9567 1098-5522