Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
10/10/2013
10/10/2013
2012
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Resumo |
Neutrophil 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-beta 2, PI3K, ERK, p38 and independent of G alpha i 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. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [474697/2008-8, 303703/2009-1] Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior National Institute for Translational Medicine National Institute for Translational Medicine South American Office for Anticancer Drug Development South American Office for Anticancer Drug Development |
Identificador |
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, WASHINGTON, v. 109, n. 2, pp. 547-552, 2012 0027-8424 http://www.producao.usp.br/handle/BDPI/34114 10.1073/pnas.1110996109 |
Idioma(s) |
eng |
Publicador |
NATL ACAD SCIENCES WASHINGTON |
Relação |
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
Direitos |
restrictedAccess Copyright NATL ACAD SCIENCES |
Palavras-Chave | #MOLECULAR TARGET #TNF-ALPHA #INFLAMMATION #CELLS #ANTAGONIST #MIGRATION #BOMBESIN #CHEMOKINES #PATHWAYS #THERAPY #MULTIDISCIPLINARY SCIENCES |
Tipo |
article original article publishedVersion |