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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schwartsmann, Gilberto Czepielewski, Rafael Sanguinetti Rizzo, Lucas Bortolotto Porto, Bárbara Nery Bonorino, Cristina Pinto, Larissa Garcia Abujamra, Ana Lúcia Cunha, Fernando De Queiroz Roesler, Rafael |
| Description | Author Affiliation: Czepielewski RS ( Laboratory of Cellular and Molecular Immunology, Biomedical Research Institute (IPB), Pontifícia Universidade Católica do Rio Grande do Sul, 90610-900, Porto Alegre, RS, Brazil.); |
| Abstract | 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-ß2, PI3K, ERK, p38 and independent of G 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Chemotaxis Immunology Inflammation Neutrophils Receptors, Bombesin Metabolism Analysis Of Variance Animals Bombesin Analogs & Derivatives Pharmacology Drug Effects Cytokines Enzyme-Linked Immunosorbent Assay Flow Cytometry Gastrin-Releasing Peptide Administration & Dosage Macrophages Mice Mice, Inbred C57BL Monocytes Peptide Fragments Antagonists & Inhibitors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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