Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

Autor(es)

Girol, Ana P. ^{[1, 2]} ; Mimura, Kallyne K. O. ^[3] ; Drewes, Carine C. ^[4] ; Boonheis, Simone M. ^[4] ; Solito, Egle ^[5] ; Farsky, Sandra H. P. ^[4] ; Gil, Cristiane D. ^[6] ; Oliani, Sonia M. ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Inst Biociencias Letras & Ciencias Exatas, Dept Biol, BR-15054000 Sao Jose Do Rio Preto - Brazil

^[2] Integrated Coll Padre Albino Fdn, Dept Phys & Biol Sci, BR-15809144 Catanduva, SP - Brazil

^[3] Univ Fed Sao Paulo, Postgrad Struct & Funct Biol, BR-04023900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo - Brazil

^[5] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ - England

^[6] Univ Fed Sao Paulo, Dept Morphol & Genet, BR-04023900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY; v. 190, n. 11, p. 5689-5701, JUN 1 2013.
• Citações Web of Science: 49

Resumo

Annexin A1 (AnxAl) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxAl and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1(-/-) mice exhibited exacerbated EIU compared with wild-type animals Immunohistochemical studies of ocular tissue showed a specific AnxAl posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxAl. In vitro studies confirmed the roles of AnxAl and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-kappa B translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxAl occur independently of the NF-kappa B signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxAl in ocular inflammation, especially uveitis, and suggest the use of AnxAl or its mimetic peptide Ac2-26 as a therapeutic approach. (AU)

• Processo FAPESP: 09/15240-1 - Efeito da proteína anti-inflamatória anexina A1 nas células epiteliais pigmentadas da retina humana (ARPE-19) após ativação pelo inflamógeno lipopolissacarídeo.
• Beneficiário: Kallyne Kioko Oliveira Mimura
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/00128-1 - Análises in vivo e in vitro da proteína anti-inflamatória anexina A1 em modelos oculares experimentais após indução por endotoxina
• Beneficiário: Sonia Maria Oliani
• Modalidade de apoio: Auxílio à Pesquisa - Regular