Beneficial effect of annexin A1 in a model of experimental allergic conjunctivitis

Autor(es)

Gimenes, Alexandre D. ^[1] ; Andrade, Teresa Raquel M. ^[1] ; Mello, Claudia B. ^[2] ; Ramos, Lisandra ^[1] ; Gil, Cristiane D. ^[1] ; Oliani, Sonia M. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, UNIFESP, Histol Lab, Dept Morfol & Genet, BR-04023900 Sao Paulo, SP - Brazil

^[2] Univ Estadual Paulista, UNESP, Dept Biol, Lab Imunomorfol, BR-15054000 Sao Jose Dos Campos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EXPERIMENTAL EYE RESEARCH; v. 134, p. 24-32, MAY 2015.
• Citações Web of Science: 17

Resumo

Annexin 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 Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/10637-3 - Efeito do tratamento farmacológico com o peptídeo mimético da proteína anexina A1 em modelo de alergia ocular
• Beneficiário: Teresa Raquel de Moraes Andrade
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/50641-0 - Estudo da proteína anti-inflamatória anexina A1 e do receptor tipo 2 para peptídeos formilados na alergia ocular
• Beneficiário: Cristiane Damas Gil
• Modalidade de apoio: Auxílio à Pesquisa - Regular