In vivo and in vitro analyses of the anti-inflammatory protein annexin A1 in experimental ocular models after induction by endotoxin

• Grant number: 11/00128-1
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Sonia Maria Oliani
• Grantee: Sonia Maria Oliani
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated researchers: Cristiane Damas Gil

Abstract

Inflammation is the main contributing factor for many ocular disorders. Pharmacological treatment of such conditions includes corticosteroids and chemotherapeutic agents, whose side effects (glaucoma and cytotoxicity) limit their use and stimulate search for new therapeutic strategies. Annexin-A1 (ANXA1), a 37 kDa protein, possesses anti-inflammatory activities, however, is rarely explored in normal and inflamed ocular tissues. Thus, we will investigate, in vivo and in vitro, the expression and the mechanism of action of endogenous ANXA1 protein in rat ocular tissues and in ARPE-19 cells derived from the human retinal pigmented epithelium (RPE) in normal and after the inflammation process induced by endotoxin. We will also investigate the possible anti-inflammatory effect of the administration of the peptide AC2-26 of the ANXA1 in those experimental conditions. Studies will be conducted by histopathological and quantitative analysis of neutrophils in ocular tissues and aqueous humor, immunohistochemical protein expression of ANXA1, ANXA1 phosphorylated in serine (ANXA1-S27-PO4) and tyrosine (ANXA1-T21-PO4) and FPR²2 in ocular tissues, immunocytochemical expressions of ANXA1 and COX-2 in ARPE-19 cells, biochemical parameters (TNF-±, IL-1², IL6, IL8, MCP1 and NO levels in supernatants of ocular tissues and/or ARPE-19 cells) and molecular studies (eletromobilility gel assay to quantify the activity of NFºB in ARPE-19 cells). The integrated results obtained from the in vivo and in vitro analyses might indicate the mechanism of action of ANXA1 in ocular inflammatory processes and provide new therapies to treat these conditions. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GIROL, ANA P.; MIMURA, KALLYNE K. O.; DREWES, CARINE C.; BOONHEIS, SIMONE M.; SOLITO, EGLE; FARSKY, SANDRA H. P.; GIL, CRISTIANE D.; OLIANI, SONIA M.. Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro. JOURNAL OF IMMUNOLOGY, v. 190, n. 11, p. 5689-5701, JUN 1 2013. (09/15240-1, 11/00128-1)

MIMURA, KALLYNE K.; TEDESCO, ROBERTO C.; CALABRESE, KATIA S.; GIL, CRISTIANE D.; OLIANI, SONIA M.. The involvement of anti-inflammatory protein, Annexin A1, in ocular toxoplasmosis. MOLECULAR VISION, v. 18, n. 163-64, p. 1583-1593, JUN 15 2012. (09/15240-1, 11/00128-1)

MIMURA‚ K.K.; TEDESCO‚ R.C.; CALABRESE‚ K.S.; GIL‚ C.D.; OLIANI‚ S.M.. The involvement of anti-inflammatory protein‚ Annexin A1‚ in ocular toxoplasmosis. MOLECULAR VISION, v. 18, p. 1583, 2012. (11/00128-1, 09/15240-1)

PAULA, JR., RUBENS; OLIANI, ANTONIO H.; VAZ-OLIANI, DENISE C. M.; D'AVILA, SOLANGE C. G. P.; OLIANI, SONIA M.; GIL, CRISTIANE D.. The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis. Journal of Molecular Histology, v. 46, n. 1, p. 33-43, FEB 2015. (11/00128-1)

PATEL, HETAL B.; KORNERUP, KRISTIN N.; SAMPAIO, ANDRE L. F.; ACQUISTO, FULVIO D.; SEED, MICHAEL P.; GIROL, ANA PAULA; GRAY, MOHINI; PITZALIS, COSTANTINO; OLIANI, SONIA M.; PERRETTI, MAURO. The impact of endogenous annexin A1 on glucocorticoid control of in ammatory arthritis. ANNALS OF THE RHEUMATIC DISEASES, v. 71, n. 11, p. 1872-1880, NOV 2012. (11/00128-1)