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dc.contributor.authorCzepielewski, Rafael Sanguinettipt_BR
dc.contributor.authorPorto, Bárbara Nerypt_BR
dc.contributor.authorRizzo, Lucas Bortolottopt_BR
dc.contributor.authorRoesler, Rafaelpt_BR
dc.contributor.authorAbujamra, Ana Lúciapt_BR
dc.contributor.authorPinto, Larissa Garciapt_BR
dc.contributor.authorSchwartsmann, Gilbertopt_BR
dc.contributor.authorCunha, Fernando de Queirozpt_BR
dc.contributor.authorBonorino, Cristina Beatriz Cazabuenapt_BR
dc.date.accessioned2016-01-20T02:40:35Zpt_BR
dc.date.issued2012pt_BR
dc.identifier.issn0027-8424pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/132070pt_BR
dc.description.abstractNeutrophil migration to inflamed sites is crucial for both the initiation of inflammation and resolution of infection, yet these cells are involved in perpetuation of different chronic inflammatory diseases. Gastrin-releasing peptide (GRP) is a neuropeptide that acts through G protein coupled receptors (GPCRs) involved in signal transmission in both central and peripheral nervous systems. Its receptor, gastrin-releasing peptide receptor (GRPR), is expressed by various cell types, and it is overexpressed in cancer cells. RC-3095 is a selective GRPR antagonist, recently found to have antiinflammatory properties in arthritis and sepsis models. Here we demonstrate that i.p. injection of GRP attracts neutrophils in 4 h, and attraction is blocked by RC-3095. Macrophage depletion or neutralization of TNF abrogates GRP-induced neutrophil recruitment to the peritoneum. In vitro, GRP-induced neutrophil migration was dependent on PLC- β2, PI3K, ERK, p38 and independent of Gαi protein, and neutrophil migration toward synovial fluid of arthritis patients was inhibited by treatment with RC-3095.We propose that GRPR is an alternative chemotactic receptor that may play a role in the pathogenesis of inflammatory disorders.en
dc.format.mimetypeapplication/pdf
dc.language.isoengpt_BR
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America. Washington. Vol. 109, no. 2 (Jan. 2012), p. 547–552pt_BR
dc.rightsOpen Accessen
dc.subjectReceptores da bombesinapt_BR
dc.subjectNeutrófilospt_BR
dc.titleGastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophilspt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000820147pt_BR
dc.type.originEstrangeiropt_BR


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