Protective effect of gastrin-releasing peptide receptor antagonist in carrageenan-induced pleural inflammation in rats

Petronilho, Fabrícia; Souza, Bruna de; Vuolo, Francieli; Benetton, César A. F.; Streck, Emílio L.; Roesler, Rafaël; Schwartsmann, Gilberto; Dal‐Pizzol, Felipe

doi:10.1007/s00011-010-0190-8

Cited by 13 publications

(8 citation statements)

References 45 publications

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“…This is in accordance with previous reports of Nmbr agonist-mediated up-regulation of Rela/p65 and Il6 expression in a mouse model of pregnancy in addition to the down-regulatory role of Nmbr antagonists [28]. Increased DNA binding activity of Rela/p65 is regarded as the key step in the onset of labor [18].…”

Section: Zhang Et Alsupporting

confidence: 93%

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

Zhang

Fei

et al. 2012

Biology of Reproduction

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The neuromedin B receptor (Nmbr) is an important physiological regulator of spontaneous activities and stress responses through different cascades as well as its autocrine and paracrine effects. Previous studies have revealed that neuromedin B (Nmb) and its receptor signal via the Rela (also known as p65)/Il6 pathway in a mouse model of pregnancy. This study investigated the mechanism of Nmbr signaling via the Rela/p65-Il6 pathway and regulation of the concentration of intracellular free calcium ([Ca(2+)](i)) during the onset of labor in primary mouse myometrial cell cultures isolated from mice in term labor. Data demonstrated Nmbr agonist-mediated upregulation of the DNA binding activity of Rela/p65, Il6 expression, and [Ca(2+)](i) in a concentration-dependent manner. Furthermore, a significant correlation was observed between DNA binding activity of Rela/p65 and Il6 expression. Moreover, this up-regulation was blocked by Nmbr and Rela/p65 knockdown, achieved by RNA interference (RNAi) technology. No significant differences were identified in the inhibition of Il6 expression as a result of Nmbr or Rela/p65 knockdown. However, significant differences were observed between the [Ca(2+)](i) in Rela/p65-specific group and that in the Nmbr-specific small interfering RNA (siRNA)-treated groups. These data demonstrated that the Nmb/Nmbr interaction in pregnant myometrial primary cells in vitro predominantly influenced uterine activity through regulation of Il6 expression via the Rela/p65 pathway, although the effects of Nmbr on [Ca(2+)](i) involved several pathways that remain to be elucidated.

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Section: Zhang Et Alsupporting

confidence: 93%

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

Zhang

Fei

et al. 2012

Biology of Reproduction

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“…It has been previously shown that GRPR antagonist RC-3095 has antiinflammatory activity in animal models of inflammation (9,10,16). We hypothesized that GRP could have proinflammatory potential, so we tested whether GRP would have a dose-dependent effect on neutrophil recruitment in vivo.…”

Section: Grp Induces Neutrophil Migration In Vivomentioning

confidence: 98%

“…After 1. 5,4,8,16,24,48, and 72 h, animals were killed, cells were cytocentrifuged, stained with Diff-Quick, and counted. cells to migrate toward GRP or leukotriene B 4 (LTB 4 ).…”

Section: Grp Has a Direct Chemoattractant Effect On Neutrophilsmentioning

confidence: 99%

Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils

Czepielewski

Porto

Rizzo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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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-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.

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“…Carrageenan-induced pleurisy is a well-characterized experimental model of inflammation, which permits the quantification of exudates and cellular migration (PETRONILHO et al, 2010). The administration of carrageenan into the pleural space leads to pleurisy, characterized by an immediate (TRAP) of V. labrusca extracts (2.5µg mL -1 ).…”

Section: Discussionmentioning

confidence: 99%

“…All efforts were made to minimize animal suffering and to use only the number of animals necessary to produce reliable scientific data. Rats (n=6) were treated intraperitoneally with saline or 10mg kg -1 body wt of V. labrusca extracts 30 minutes before induction of peritonitis through injection of 0.2mL of carrageenan 1% (PETRONILHO et al, 2010). Four hours after inducing inflammation, animals were euthanized, and pleural exudates from each animal were harvested by washing the pleural cavity with 2mL of sterile saline solution for measuring total and differential cell count, lactate dehydrogenase activity (LDH), TNF-alpha levels and total proteins.…”

Section: Methodsmentioning

confidence: 99%

Antioxidant and anti-inflammatory activities of winery wastes seeds of Vitis labrusca

et al. 2011

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Protective effect of gastrin-releasing peptide receptor antagonist in carrageenan-induced pleural inflammation in rats

Abstract: The present findings suggest that GRP plays a role in acute inflammation that can be related with the reduction of oxidative damage and that it could be effective in therapeutic applications.

Cited by 13 publications

References 45 publications

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils

Antioxidant and anti-inflammatory activities of winery wastes seeds of Vitis labrusca

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