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- ItemSomente MetadadadosBeneficial effect of annexin A1 in a model of experimental allergic conjunctivitis(Elsevier B.V., 2015-05-01) Gimenes, Alexandre D. [UNIFESP]; Andrade, Teresa Raquel M. [UNIFESP]; Mello, Claudia B.; Ramos, Lisandra [UNIFESP]; Gil, Cristiane D. [UNIFESP]; Oliani, Sonia M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Estadual PaulistaAnnexin A1 (ANXA1), a 37 kDa glucocorticoid-regulated protein, is a potent anti-inflammatory mediator effective in terminating acute inflammatory response, and its role in allergic settings has been poorly studied. the aim of this investigation was to evaluate the mechanism of action of ANXA1 in intraocular inflammation using a classical model of ovalbumin (OVA)-induced allergic conjunctivitis (AC). OVA-immunised Balb/c mice, wild-type (WT) and ANXA1-deficient (AnxA1(-/-)), were challenged with eye drops containing OVA on days 14-16 with a subset of WT animals pretreated intraperitoneally with the peptide AC(2-26) (N-terminal region of ANXA1) or dexamethasone (DEX). After 24 h of the last ocular challenge, WT mice treated with Ac2-26 and DEX had significantly reduced clinical signs of conjunctivitis (chemosis, conjunctival hyperaemia, lid oedema and tearing), plasma IgE levels, leukocyte (eosinophil and neutrophil) influx and mast cell degranulation in the conjunctiva compared to WT controls. These anti-inflammatory effects of DEX were associated with high endogenous levels of ANXA1 in the ocular tissues as detected by immunohistochemistry. Additionally, AC(2-26) administration was effective to reduce IL-2, IL-4, IL-10, IL-13, eotaxin and RANTES in the eye and lymph nodes compared to untreated WT animals. the lack of ANXA1 produced an exacerbated allergic response as detected by the density of the inflammatory cell influx to the conjunctiva and the cytokine/chemokine release. These different effects observed for Ac2-26 were correlated with diminished level of activated ERK at 24 h in the ocular tissues compared to untreated OVA group. Our findings demonstrate the protective effect of ANXA1 during the inflammatory allergic response suggesting this protein as a potential target for new ocular inflammation therapies. (C) 2015 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosFluctuation of annexin-A1 positive mast cells in chronic granulomatous inflammation(Birkhauser Verlag Ag, 2008-10-01) Oliani, S. M. [UNIFESP]; Ciocca, G. A. Panin; Pimentel, T. A. [UNIFESP]; Damazo, Amilcar Sabino [UNIFESP]; Gibbs, L.; Perretti, M.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); William Harvey Res InstObjective: We have applied here a model of chronic granulomatous inflammation to study the profile of mast cell activation and their expression of annexin-A1 in the nodular lesion.Materials: Granulomatous inflammation was induced by injection of croton oil and Freund's complete adjuvant (CO/FCA) into the dorsal air-pouches of mice. Skin tissue samples were collected from control group (24 h time-point; i.e. before disease development) and 7, 14, 21, 28 and 42 days post-CO/FCA treatment.Results: Histopathological analyses revealed an on-going inflammation characterized by an increased number of activated mast cells at sites of the chronic inflammatory reaction in all experimental groups. Immunohistochemical analysis showed skin mast cells highly immunoreactive for annexin-A1, both at an initial (day 7) and a delayed (day 28) phase of the inflammatory reaction.Conclusions: the observed time-dependent modulation of mast cell activation, during the granulomatous injury, indicates that multiple pathways centred on annexin-A1 might become activated at different stages of this chronic inflammatory response, including the delayed and pro-resolving phase.