title: Beneficial effect of annexin A1 in a model of experimental allergic conjunctivitis.
abstract: 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 Ac2-26 (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, Ac2-26 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.
authors: UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, 04023-900 São Paulo, São Paulo, Brazil.
authors: Alexandre D
authors: AD
authors: Gimenes
authors: UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, 04023-900 São Paulo, São Paulo, Brazil.
authors: Teresa Raquel M
authors: TR
authors: Andrade
authors: UNESP - Universidade Estadual Paulista, Laboratório de Imunomorfologia, Departamento de Biologia, 15054-000 São José do Rio Preto, São Paulo, Brazil.
authors: Cláudia B
authors: CB
authors: Mello
authors: UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, 04023-900 São Paulo, São Paulo, Brazil.
authors: Lisandra
authors: L
authors: Ramos
authors: UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, 04023-900 São Paulo, São Paulo, Brazil.
authors: Cristiane D
authors: CD
authors: Gil
authors: UNIFESP - Universidade Federal de São Paulo, Laboratório de Histologia, Departamento de Morfologia e Genética, 04023-900 São Paulo, São Paulo, Brazil; UNESP - Universidade Estadual Paulista, Laboratório de Imunomorfologia, Departamento de Biologia, 15054-000 São José do Rio Preto, São Paulo, Brazil. Electronic address: smoliani@ibilce.unesp.br.
authors: Sonia M
authors: SM
authors: Oliani
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000627:therapeutic use*; D015153:Blotting, Western; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004804:Eosinophils / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000097:blood; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000633:toxicity; D010455:Peptides / Q000627:therapeutic use*
chemical_list: D017305:Annexin A1; D016207:Cytokines; D005938:Glucocorticoids; D010455:Peptides; C096153:annexin A1 peptide (2-26); D007073:Immunoglobulin E; D003907:Dexamethasone; D010047:Ovalbumin
keywords: ERK; Eosinophils; Lipocortin 1; Mast cells; Ocular allergy; Th1/Th2 cytokines