Navegando por Palavras-chave "S100A9"

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    Analgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibition
    (Wiley-Blackwell, 2009-08-01) Dale, Camila Squarzoni; Altier, Christophe; Cenac, Nicolas; Giorgi, Renata; Juliano, Maria Aparecida [UNIFESP]; Juliano, Luiz [UNIFESP]; Zamponi, Gerald W.; Vergnolle, Nathalie; INSERM; Univ Toulouse 3; Univ Calgary; Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
    Calcium-binding protein S100A9 and its C-terminus peptide (mS100A9p) are anti-inflammatory and induce antinociception in rodents. We investigated the mechanisms involved in this effect, and whether they depend or not on the anti-inflammatory properties of mS100A9p. in mice, mS100A9p inhibited thermal and mechanical hyperalgesia and allodynia induced by either carrageenan or formalin, without interfering with paw edema. mS100A9p also inhibited myeloperoxidase activity (MPO), a marker of granulocyte infiltration, induced by carrageenan, but increased MPO after formalin intraplantar injection. the in vivo analgesic properties of mS100A9p were independent of opioid receptor activation. Calcium flux into dorsal root ganglia neurons induced by KCl was inhibited by mS100A9p, suggesting that this protein is able to inhibit signaling, in sensory neurons. the inhibitory effects of mS100A9p on primary afferent signaling were neither due to intracellular calcium store inhibition nor to calcium chelating properties. However, mS100A9p was able to inhibit calcium currents carried by transiently expressed N-type, but not L-type calcium channels, as demonstrated both by gene transfection techniques and electrophysiology. These data demonstrate that mS100A9p interferes with mechanisms involved in nociception, hyperalgesia and calcium signaling in sensory neurons, modulating primary afferent nociceptive signal by inhibiting activation of N-type voltage operated calcium channels.
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    Antinociceptive effect of the C-terminus of murine S100A9 protein on experimental neuropathic pain
    (Elsevier B.V., 2008-10-01) Paccola, Carina Cicconi; Gutierrez, Vanessa Pacciari; Longo, Ingrid; Juliano, Luiz [UNIFESP]; Juliano, Maria Aparecida [UNIFESP]; Giorgi, Renata; Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
    The synthetic peptide identical to the C-terminus of murine S100A9 protein (mS100A9p) has antinociceptive effect on different acute inflammatory pain models. in this study, the effect of mS100A9p was investigated on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Hyperalgesia, allodynia, and spontaneous pain were assessed to evaluate nociception. These three signs were detected as early as 2 days after sciatic nerve constriction and lasted for over 14 days after CCI. Rats were treated with different doses of mS100A9p by intraplantar, oral, or intrathecal routes on day 14 after CCI, and nociception was evaluated 1 h later. These three routes of administration blocked hyperalgesia, allodynia and spontaneous pain. the duration of the effect of mS100A9p depends on the route used and phenomenon analyzed. Moreover, intraplantar injection of mS100A9p in the contralateral paw inhibited the hyperalgesia on day 14 days after CCI the results obtained herein demonstrate the antinociceptive effect of the C-terminus of murine S100A9 protein on experimental neuropathic pain, suggesting a potential therapeutic use for it in persistent pain syndromes, assuming that tolerance does not develop to mS100A9p. (C) 2008 Elsevier Inc. All rights reserved.
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    The C-terminus of murine S100A9 inhibits hyperalgesia and edema induced by jararhagin
    (Elsevier B.V., 2004-01-01) Dale, C. S.; Goncalves, LRC; Juliano, L.; Juliano, M. A.; Silva, AMM da; Giorgi, R.; Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
    The effect of a synthetic peptide (H-92-G(110)) identical to the C-terminus of murine S100A9 (mS100A9p) was investigated on hyperalgesia and edema induced by either jararhagin or papain in the rat paw. mS100A9p not only reverted hyperalgesia and edema induced by jararhagin, but also the highest concentration induced antinociception. Hemorrhage induced by jararhagin and its hydrolytic activity were inhibited by mS100A9p. These data suggest that mS100A9p might block jararhagin-induced hyperalgesia and edema by inhibiting jararhagin catalytic activity, since papain-induced hyperalgesia and edema were not inhibited by mS100A9p. (C) 2004 Elsevier Inc. All rights reserved.
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    The C-terminus of murine S100A9 inhibits spreading and phagocytic activity of adherent peritoneal cells
    (Birkhauser Verlag Ag, 2005-05-01) Pagano, R. L.; Sampaio, S. C.; Juliano, L.; Juliano, M. A.; Giorgi, R.; Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
    Objective and design: in the present study, the effect of a synthetic peptide (H-92-G(102)) identical to the C-terminus of murine S100A9 (mS100A9p) was investigated on adherent peritoneal cell function.Materials and methods: for in vitro assays, peritoneal cells were obtained from the abdominal cavity of mice and incubated, with the different concentrations of mS100A9p, for 1 h, and then their spreading and phagocytosis activities were evaluated. for ex-vivo assays, cells obtained from animals treated for 1 h with the peptide were submitted to the mannose-receptor phagocytosis assay. Shorter homologue peptides to the C-terminus of mS100A9p were also evaluated on in vitro phagocytosis assays of Candida albicans particles.Results: mS100A9p reduced both the spreading index and phagocytic activity, in vitro and ex-vivo, independent of the receptor evaluated. the homologue peptide corresponding to the H-92-E-97 region of mS100A9p, the zinc-binding motif, was responsible for such an effect.Conclusion: These results suggest a modulator effect of the C-terminus of S100A9 protein on the function of adherent peritoneal cells.
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    The C-terminus of murine S100A9 protein inhibits hyperalgesia induced by the agonist peptide of protease-activated receptor 2 (PAR(2))
    (Nature Publishing Group, 2006-10-01) Dale, C. S.; Cenac, N.; Britto, L. R. G.; Juliano, Maria Aparecida [UNIFESP]; Juliano, Luiz [UNIFESP]; Vergnolle, N.; Giorgi, R.; Univ Calgary; Butantan Inst; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Background and purpose: S100A9 protein induces anti-nociception in rodents, in different experimental models of inflammatory pain. Herein, we investigated the effects of a fragment of the C-terminus of S100A9 (mS100A9p), on the hyperalgesia induced by serine proteases, through the activation of protease-activated receptor-2 (PAR(2)).Experimental approach: Mechanical and thermal hyperalgesia induced by PAR(2) agonists (SLIGRL-NH2 and trypsin) was measured in rats submitted to the paw pressure or plantar tests, and Egr-1 expression was determined by immunohistochemistry in rat spinal cord dorsal horn. Calcium flux in human embryonic kidney cells (HEK), which naturally express PAR(2), in Kirsten virus-transformed kidney cells, transfected (KNRK-PAR(2)) or not (KNRK) with PAR(2), and in mouse dorsal root ganglia neurons (DRG) was measured by fluorimetric methods.Key results: mS100A9p inhibited mechanical hyperalgesia induced by trypsin, without modifying its enzymatic activity. Mechanical and thermal hyperalgesia induced by SLIGRL-NH2 were inhibited by mS100A9p. SLIGRL-NH2 enhanced Egr-1 expression, a marker of nociceptor activation, and this effect was inhibited by concomitant treatment with mS100A9p. mS100A9p inhibited calcium mobilization in DRG neurons in response to the PAR(2) agonists trypsin and SLIGRL-NH2, but also in response to capsaicin and bradykinin, suggesting a direct effect of mS100A9 on sensory neurons. No effect on the calcium flux induced by trypsin or SLIGRL in HEK cells or KNRK-PAR(2) cells was observed.Conclusions and implications: These data demonstrate that mS100A9p interferes with mechanisms involved in nociception and hyperalgesia and modulates, possibly directly on sensory neurons, the PAR(2)-induced nociceptive signal.
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    Effect of the C-terminus of murine S100A9 protein on experimental nociception
    (Elsevier B.V., 2006-11-01) Dale, Camila Squarzoni; Pagano, Rosana de Lima; Paccola, Carina Cicconi; Pinotti-Guirao, Tatiana; Juliano, Maria Aparecida; Juliano, Luiz; Giorgi, Renata; Butantan Inst; Universidade Federal de São Paulo (UNIFESP)
    Calcium-binding protein S100A9 induces antinociception in mice evaluated by the writhing test. Similarly, a peptide identical to the C-terminus of murine S100A9 (mS100A9p) inhibits the hyperalgesia induced by jararhagin, a metalloprotease. Thus, we investigated the effect of mS100A9p on different models used to evaluate nociception. mS100A9p induced a dose-dependent inhibitory effect on the writhing test, and on mechanical hyperalgesia induced by carrageenan. mS100A9p inhibited thermal hyperalgesia induced by carrageenan. mS100A9p did not modify the nociceptive response in hot plate or tail-flick tests. These data demonstrate that the C-terminus of S100A9 protein interferes with control mechanisms of inflammatory pain. (c) 2006 Elsevier Inc. All rights reserved.
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    Involvement of proteinase-activated receptors 1 and 2 in spreading and phagocytosis by murine adherent peritoneal cells: Modulation by the C-terminal of S100A9 protein
    (Elsevier B.V., 2010-02-25) Pagano, Rosana L.; Sampaio, Sandra C.; Juliano, Maria A. [UNIFESP]; Juliano, Luiz [UNIFESP]; Giorgi, Renata; Butantan Inst; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Proteinase-activated receptors (PAR) are widely recognized for their modulatory properties in inflammatory and immune responses; however, their direct role on phagocyte effector functions remains unknown. S100A9, a protein secreted during inflammatory responses, deactivates activated peritoneal macrophages, and its C-terminal portion inhibits spreading and phagocytosis of adherent peritoneal cells. Herein, the effect of PAR1 and PAR2 agonists was investigated on spreading and phagocytosis by adherent peritoneal cells, as well as the ability of murine C-terminal of S100A9 peptide (mS100A9p) to modulate this effect. Adherent peritoneal cells obtained from mouse abdominal cavity were incubated with PAR1 and PAR2 agonists and spreading and phagocytosis of Candida albicans particles were evaluated. PAR1 agonists increased both the spreading and the phagocytic activity, but PAR2 agonists only increased the spreading index. mS100A9p reverted both the increased spreading and phagocytosis induced by PAR1 agonists, but no interference in the increased spreading induced by PAR2 agonists was noticed. the shorter homologue peptide to the C-terminal of mS100A9p, corresponding to the H(92)-E(97) region, also reverted the increased spreading and phagocytosis induced by PAR1 agonists. These findings show that proteinase-activated receptors have an important role for spreading and phagocytosis of adherent peritoneal cells, and that the pepticle corresponding to the C-terminal of S100A9 protein is a remarkable candidate for use as a novel compound to modulate PAR1 function. (C) 2009 Elsevier B.V. All rights reserved.
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    Macrophage suppression following phagocytosis of apoptotic neutrophils is mediated by the S100A9 calcium-binding protein
    (Elsevier B.V., 2010-05-01) De Lorenzo, B. H. P. [UNIFESP]; Godoy, L. C.; Novaes e Brito, R. R. [UNIFESP]; Pagano, R. L.; Amorim-Dias, M. A. [UNIFESP]; Grosso, D. M.; Lopes, J. D. [UNIFESP]; Mariano, M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); MIT; Universidade de São Paulo (USP); Hosp Alemao Oswaldo Cruz; Univ Estadual Paulista
    The clearance of apoptotic cells by phagocytes is a fundamental process during tissue remodeling and resolution of inflammation. in turn, the phagocytosis of apoptotic cells generates signals that suppress pro-inflammatory activation of macrophages. These events occur during the resolution phase of inflammation and therefore the malfunctioning of this process may lead to inflammation-related tissue damage. Here, we demonstrate that the calcium-binding protein S100A9, normally abundant in the cytoplasm of neutrophils and also released by apoptotic neutrophils, is involved in the suppression of macrophages after the uptake of apoptotic neutrophils. Both, spontaneous and induced production of inflammatory species (nitric oxide, hydrogen peroxide and TNF-alpha) as well as the phagocytic activity were inhibited when macrophages were in presence of apoptotic neutrophils, conditioned medium from neutrophil cultures or a peptide corresponding to the C-terminal region of S100A9 protein. On the other hand, macrophages kept in the conditioned medium of neutrophils that was previously depleted of S100A9 were shown to resume the activated status. Finally, we demonstrate that the calcium-binding property of S100A9 might play a role in the suppression process, since the stimulation of intracellular calcium release with ionomycin significantly reversed the effects of the uptake of apoptotic neutrophils in macrophages. in conclusion, we propose that S100A9 is a novel component of the regulatory mechanisms of inflammation, acting side-by-side with other suppressor factors generated upon ingestion of apoptotic cells. (C) 2009 Elsevier GmbH. All rights reserved.