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- ItemSomente MetadadadosInvolvement 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.
- ItemSomente MetadadadosMechanisms underlying the nociceptive and inflammatory responses induced by trypsin in the mouse paw(Elsevier B.V., 2008-02-26) Paszcuk, Ana Flavia; Quintao, Nara L. M.; Fernandes, Elizabeth S.; Juliano, Luiz [UNIFESP]; Chapman, Kevin; Andrade-Gordon, Patricia; Campos, Maria Martha; Vergnolle, Nathalie; Calixto, Joao B.; Universidade Federal de Santa Catarina (UFSC); Universidade Federal de São Paulo (UNIFESP); Pontificia Univ Catolica Rio Grande do Sul; Univ CalgaryIt has been demonstrated that trypsin is able to evoke the classical signals of inflammation, mainly via the activation of proteinase-activated receptor-2 (PAR-2). This study was designed to evaluate the inflammatory and nociceptive responses caused by trypsin injection in the mouse paw. Trypsin produced a dose- and time-related paw edema, a response that was markedly reduced in PAR-2-deficient mice compared to wild-type mice, particularly at the early time-points after trypsin injection. in addition, trypsin produced an increase in myeloperoxidase (MPO) activity, which was significantly reduced in PAR-2-deficient mice. the injection of trypsin into the mouse paw also elicited a dose- and time-dependent spontaneous nociception, as well as thermal and mechanical hypernociceptive responses, which were consistently decreased in mice with genetic deletion of PAR-2. Pharmacological evaluation revealed that edema formation and spontaneous nociception caused by trypsin injection in the mouse paw are mediated by a complex range of mediators. Both edema and nociception seem to rely on the production of neuropeptides, probably involving C-fibre activation and vanilloid receptor-1 (TRPV1), besides the stimulation of kinin B-2 receptors. Edematogenic response is also likely related to the production of cyclooxygenase (COX) metabolites, whereas the mast cell activation appears to be greatly associated to spontaneous nociception. Altogether, the present results indicate that trypsin-induced edema and nociception in the mouse paw represent multi-mediated responses that are largely, but not exclusively, related to the activation of PAR-2. These pieces of evidence provide new insights on the role of trypsin in pain and inflammation. (C) 2007 Elsevier B.V. All rights reserved.