A crucial role for TNF‐α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5

Vieira, SM; Lemos, H.C.; Grespan, Renata; Napimoga, Marcelo Henrique; Dal-Secco, Daniela; Freitas, Aguinaldo de; Cunha, Telma F.; Verri, Waldiceu A.; Souza-Junior, DA; Jamur, M.C.; Fernandes, Karin Sá; Oliver, Constance; Silva, João; Teixeira, M.M.; Cunha, Fernando

doi:10.1111/j.1476-5381.2009.00367.x

Cited by 154 publications

(123 citation statements)

References 53 publications

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“…The direct effect is demonstrated by the in vitro experiments, and the checkerboard analysis indicates that it has a chemotactic effect, and not simply a chemokinetic one. In vivo, besides acting directly on neutrophils, GRP would act on macrophages, inducing TNF-α production, leading to up-regulation of adhesion molecules that are necessary for neutrophil extravasation (17).…”

Section: Discussionmentioning

confidence: 99%

“…TNF-α is one of the major cytokines released by macrophages in response to inflammatory stimuli, enhancing neutrophil migration by increasing the expression of adhesion molecules on endothelial cells and neutrophils, facilitating cell arrival to inflamed sites (17). To investigate the role of TNF-α in our system, we pretreated mice with a therapeutic TNF-α-specific neutralizing antibody (infliximab), a chimeric (mouse/human) antibody that cross-reacts with murine TNF-α (18).…”

Section: Grp-induced Neutrophil Recruitment In Vivo Depends On Macropmentioning

confidence: 99%

“…An alternative explanation for our observations was that GRP induced chemokine production by macrophages, which in turn could up-regulate TNF-α production in vivo, enhancing GRP-induced neutrophil recruitment. Chemokines peak earlier than some cytokines (17) and it was possible that a dose other than 1 nM was necessary to induce these mediators in macrophages/ monocytes, so we used a range of concentrations of GRP for stimulation (10-0.001 nM), for 2 h. Supernatants were analyzed for TNF-α, KC/IL-8, MIP-2, and MCP-1 production. Results shown in Fig.…”

Section: Grp-induced Neutrophil Recruitment In Vivo Depends On Macropmentioning

confidence: 99%

“…Chemokines (17) and leukotrienes (21) and molecules released by damaged tissues (22,23) act as chemoattractants, acting directly on neutrophils to induce migration. We investigated whether GRP, a neuropeptide, would induce neutrophils to migrate up a gradient of GRP in vitro, in a Transwell system.…”

Section: Grp Has a Direct Chemoattractant Effect On Neutrophilsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Grp-induced Neutrophil Recruitment In Vivo Depends On Macropmentioning

confidence: 99%

Section: Grp-induced Neutrophil Recruitment In Vivo Depends On Macropmentioning

confidence: 99%

Section: Grp Has a Direct Chemoattractant Effect On Neutrophilsmentioning

confidence: 99%

See 2 more Smart Citations

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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“…These cytokines are crucial in inflammation in a manner that they are virtually involved in every type of inflammation Valério et al, 2007;Verri et al, 2006;Verri et al, 2007;Verri et al, 2010;Vieira et al, 2009). Moreover, TNFα and IL-1β are clinically-proved therapeutic targets to diminish inflammation as observed in rheumatoid arthritis with infliximab, etanercept, anakinra and other anti-cytokine antibodies, soluble receptors and receptor antagonists Verri et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tephrosia sinapou extract reduces inflammatory leukocyte recruitment in mice: effect on oxidative stress, nitric oxide and cytokine production

Martínez

Zarpelon

Zimermann

et al. 2012

Rev. bras. farmacogn.

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Abstract:Tephrosia toxicaria (Sw.) Pers., which is currently known as T. sinapou (Buc'hoz) A. Chev., Fabaceae, is a source of compounds such as fl avonoids, however, few studies addressed the anti-infl ammatory and antioxidant effects of T. sinapou. Therefore, we evaluated the antioxidant mechanisms of the T. sinapou ethyl acetate extract in vitro, and whether the extract affects leukocyte recruitment in four models of infl ammation and the involvement of nitric oxide and cytokines in its mechanism. In vitro, it was observed that the extract presented hydrogen donating ability to 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH • ), 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS + ), and also effi ciently inhibited iron-dependent and independent lipid peroxidation and iron chelation assays. In vivo, it inhibited the recruitment of total leukocytes and neutrophil induced by carrageenin, zymosan, glycogen and lipopolysaccharide in the peritoneal cavity of mice. Two mechanisms were detected: 1) T. sinapou effect on leukocyte recruitment depends on nitric oxide since was dose-dependently inhibited by treatment with L-NAME (nitric oxide synthase inhibitor), and 2) the extract also inhibited the production of crucial cytokines for the leukocyte recruitment; tumor necrosis factor α and interleukin-1β. Concluding, T. sinapou ethyl acetate extract reduces oxidative stress in vitro, and infl ammatory leukocyte recruitment by a mechanism related to inhibition of cytokine production, and in a nitric oxide dependent manner in vivo.

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Enhancing tristetraprolin activity reduces the severity of cigarette smoke‐induced experimental chronic obstructive pulmonary disease

et al. 2019

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Objective. Chronic obstructive pulmonary disease (COPD) is a progressive disease that causes significant mortality and morbidity worldwide and is primarily caused by the inhalation of cigarette smoke (CS). Lack of effective treatments for COPD means there is an urgent need to identify new therapeutic strategies for the underlying mechanisms of pathogenesis. Tristetraprolin (TTP) encoded by the Zfp36 gene is an anti-inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD.Methods. Here, we identify a novel protective role for TTP in CSinduced experimental COPD using Zfp36 aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNAdestabilising factor. TTP wild-type (Zfp36 +/+ ) and Zfp36 aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed. Results. After four days of CS exposure, Zfp36 aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild-type controls. After eight weeks, Zfp36 aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema-like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL (S) , and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS-induced experimental COPD were ameliorated. Conclusion. Collectively, our ª

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A crucial role for TNF‐α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5

Cited by 154 publications

References 53 publications

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

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

Tephrosia sinapou extract reduces inflammatory leukocyte recruitment in mice: effect on oxidative stress, nitric oxide and cytokine production

Enhancing tristetraprolin activity reduces the severity of cigarette smoke‐induced experimental chronic obstructive pulmonary disease

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