Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.2353/ajpath.2006.050658 http://hdl.handle.net/11449/231011 |
Resumo: | We have investigated the specific contribution of protease-activated receptor-2 (PAR2) to host defense during Porphyromonas gingivalis infection. Culture supernatants from P. gingivalis strains 33277 and W50 provoked Ca2+ mobilization in cells transfected with PAR2 (PAR2-KNRK) and desensitized the subsequent responses to PAR 2-selective agonist. In addition, culture supernatants of P. gingivalis E8 (RgpA/RgpB double knockout) did not cause calcium response in PAR2-KNRK cells, evidencing the involvement of the arginine-specific cysteine proteases RgpA and RgpB in PAR2 activation by P. gingivalis. Injection of P. gingivalis into mouse subcutaneous chambers provoked an increased proteolytic activity, which was inhibited by serine protease inhibitors. Fluids collected from chambers of P. gingivalis-injected mice were able to activate PAR2 and this activation was inhibited by serine protease inhibitors. P. gingivalis inoculation into subcutaneous chambers of wild-type mice induced an inflammatory response that was inhibited by a serine protease inhibitor and was significantly reduced in PAR2-deficient mice. Finally, mice orally challenged with P. gingivalis developed alveolar bone loss, which was significantly reduced in PAR2-deficient mice at 42 and 60 days after P. gingivalis infection. We conclude that PAR2 is activated on P. gingivalis infection, in which it plays an important role in the host inflammatory response. Copyright © American Society for Investigative Pathology. |
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Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infectionWe have investigated the specific contribution of protease-activated receptor-2 (PAR2) to host defense during Porphyromonas gingivalis infection. Culture supernatants from P. gingivalis strains 33277 and W50 provoked Ca2+ mobilization in cells transfected with PAR2 (PAR2-KNRK) and desensitized the subsequent responses to PAR 2-selective agonist. In addition, culture supernatants of P. gingivalis E8 (RgpA/RgpB double knockout) did not cause calcium response in PAR2-KNRK cells, evidencing the involvement of the arginine-specific cysteine proteases RgpA and RgpB in PAR2 activation by P. gingivalis. Injection of P. gingivalis into mouse subcutaneous chambers provoked an increased proteolytic activity, which was inhibited by serine protease inhibitors. Fluids collected from chambers of P. gingivalis-injected mice were able to activate PAR2 and this activation was inhibited by serine protease inhibitors. P. gingivalis inoculation into subcutaneous chambers of wild-type mice induced an inflammatory response that was inhibited by a serine protease inhibitor and was significantly reduced in PAR2-deficient mice. Finally, mice orally challenged with P. gingivalis developed alveolar bone loss, which was significantly reduced in PAR2-deficient mice at 42 and 60 days after P. gingivalis infection. We conclude that PAR2 is activated on P. gingivalis infection, in which it plays an important role in the host inflammatory response. Copyright © American Society for Investigative Pathology.Department of Pharmacology and Therapeutics Faculty of Medicine University of Calgary, Calgary, Alta.Canadian Institute for Health Research Group in Matrix Dynamics Dental Research Institute University of Toronto, Toronto, Ont.Department of Periodontology and Oral Pathology Dental School of Araraquara State University of São Paulo, Araraquara, São PauloDepartment of Dermatology Ludwig Boltzman Institute for Immunobiology of the Skin University Hospital, MuensterDrug Discovery Johnson and Johnson Pharmaceutical Research and Development, Spring House, PAPharmacology and Therapeutics Faculty of Medicine University of Calgary, 3330 Hospital Dr., NW, Calgary, Alta. T2N 4N1University of CalgaryUniversity of TorontoUniversidade de São Paulo (USP)University HospitalJohnson and Johnson Pharmaceutical Research and DevelopmentHolzhausen, MarinellaSpolidorio, Luis CarlosEllen, Richard P.Jobin, Marie-ClaudeSteinhoff, MartinAndrade-Gordon, PatriciaVergnolle, Nathalie2022-04-29T08:43:13Z2022-04-29T08:43:13Z2006-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1189-1199http://dx.doi.org/10.2353/ajpath.2006.050658American Journal of Pathology, v. 168, n. 4, p. 1189-1199, 2006.0002-9440http://hdl.handle.net/11449/23101110.2353/ajpath.2006.0506582-s2.0-33645458377Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAmerican Journal of Pathologyinfo:eu-repo/semantics/openAccess2022-04-29T08:43:14Zoai:repositorio.unesp.br:11449/231011Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:43:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
title |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
spellingShingle |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection Holzhausen, Marinella |
title_short |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
title_full |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
title_fullStr |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
title_full_unstemmed |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
title_sort |
Protease-activated receptor-2 activation: A major role in the pathogenesis of Porphyromonas gingivalis infection |
author |
Holzhausen, Marinella |
author_facet |
Holzhausen, Marinella Spolidorio, Luis Carlos Ellen, Richard P. Jobin, Marie-Claude Steinhoff, Martin Andrade-Gordon, Patricia Vergnolle, Nathalie |
author_role |
author |
author2 |
Spolidorio, Luis Carlos Ellen, Richard P. Jobin, Marie-Claude Steinhoff, Martin Andrade-Gordon, Patricia Vergnolle, Nathalie |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
University of Calgary University of Toronto Universidade de São Paulo (USP) University Hospital Johnson and Johnson Pharmaceutical Research and Development |
dc.contributor.author.fl_str_mv |
Holzhausen, Marinella Spolidorio, Luis Carlos Ellen, Richard P. Jobin, Marie-Claude Steinhoff, Martin Andrade-Gordon, Patricia Vergnolle, Nathalie |
description |
We have investigated the specific contribution of protease-activated receptor-2 (PAR2) to host defense during Porphyromonas gingivalis infection. Culture supernatants from P. gingivalis strains 33277 and W50 provoked Ca2+ mobilization in cells transfected with PAR2 (PAR2-KNRK) and desensitized the subsequent responses to PAR 2-selective agonist. In addition, culture supernatants of P. gingivalis E8 (RgpA/RgpB double knockout) did not cause calcium response in PAR2-KNRK cells, evidencing the involvement of the arginine-specific cysteine proteases RgpA and RgpB in PAR2 activation by P. gingivalis. Injection of P. gingivalis into mouse subcutaneous chambers provoked an increased proteolytic activity, which was inhibited by serine protease inhibitors. Fluids collected from chambers of P. gingivalis-injected mice were able to activate PAR2 and this activation was inhibited by serine protease inhibitors. P. gingivalis inoculation into subcutaneous chambers of wild-type mice induced an inflammatory response that was inhibited by a serine protease inhibitor and was significantly reduced in PAR2-deficient mice. Finally, mice orally challenged with P. gingivalis developed alveolar bone loss, which was significantly reduced in PAR2-deficient mice at 42 and 60 days after P. gingivalis infection. We conclude that PAR2 is activated on P. gingivalis infection, in which it plays an important role in the host inflammatory response. Copyright © American Society for Investigative Pathology. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-01-01 2022-04-29T08:43:13Z 2022-04-29T08:43:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.2353/ajpath.2006.050658 American Journal of Pathology, v. 168, n. 4, p. 1189-1199, 2006. 0002-9440 http://hdl.handle.net/11449/231011 10.2353/ajpath.2006.050658 2-s2.0-33645458377 |
url |
http://dx.doi.org/10.2353/ajpath.2006.050658 http://hdl.handle.net/11449/231011 |
identifier_str_mv |
American Journal of Pathology, v. 168, n. 4, p. 1189-1199, 2006. 0002-9440 10.2353/ajpath.2006.050658 2-s2.0-33645458377 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
American Journal of Pathology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1189-1199 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1803649308174581760 |