Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 190, n. 11, p. 5689-5701, JUN 1 2013.
Web of Science Citations: 49
Abstract

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)

FAPESP's process: 09/15240-1 - Anti-inflammatory effect of annexin A1 protein in human retinal pigment epithelium (ARPE-19) after activation by inflammogen lipopolysaccharide.
Grantee:Kallyne Kioko Oliveira Mimura
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 11/00128-1 - In vivo and in vitro analyses of the anti-inflammatory protein annexin A1 in experimental ocular models after induction by endotoxin
Grantee:Sonia Maria Oliani
Support Opportunities: Regular Research Grants