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Role of formyl peptide receptors and mimetic peptide of Annexin A1 in the ocular allergy

Grant number: 15/22944-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Cristiane Damas Gil
Grantee:Mariana Prado Marmorato
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Allergic conjunctivitis (AC) is a complex disease of the immune system involving an inflammatory response and consequent ocular disorders and may lead to decreased visual acuity and blindness. In the treatment of intraocular inflammation in general, glucocorticoids are administered drugs whose side effects stimulate search for new therapeutic strategies. In this respect, the protein annexin A1 (ANXA1) acts as a potent endogenous mediator of anti-inflammatory actions that can be activated by formyl peptide receptors (fprs). However, the expression of ANXA1 and fprs in normal and inflamed ocular tissues has been little explored. Thus, we will analyze in an experimental model of murine AC, the expression of fpr1 and fpr2 receptors and their relation to ANXA1 protein. Male Balb/c mice will be immunized on days 0 and 7, subcutaneously with ovalbumin (OVA; 5 ug) and on days 14, 15 and 16 will receive direct instillation into the conjunctival sac of 250 ug OVA in 10 uL of sterile saline. Another group of sensitized animals will be pretreated i.p. from 14 to 16 with the mimetic peptide of ANXA1 (Ac2-26; 100 mg/Kg), with Boc2 (10 mg/animal), an fpr antagonist, or Ac2-26+Boc2 diluted in 0.1 mL saline. Control animals will receive only saline. After 24 hours of last challenge with OVA, the animals will be euthanized for collection of blood, eyes, eyelids and spleen. The studies will be conducted through: dosage of IgE anti-ovalbumin by ELISA blood; morphological and quantitative analysis of mast cells and eosinophils in the eyelid conjunctiva; immunohistochemistry to detect fpr1 and fpr2 expression in eyelids; Western blotting to detect the fprs, mitogen-activated protein kinases (MAPK), mouse mast cell protease 6 and eosinophil peroxidase expression in the eyes and spleen homogenates. The results will contribute to better understanding of the role of fprs and their relationship with ANXA1 in allergic ocular inflammation.

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Scientific publications
(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)
MARMORATO, MARIANA PRADO; GIMENES, ALEXANDRE DANTAS; COSTA ANDRADE, FRANS EBERTH; OLIANI, SONIA MARIA; GIL, CRISTIANE DAMAS. Involvement of the annexin A1-Fpr anti-inflammatory system in the ocular allergy. European Journal of Pharmacology, v. 842, p. 298-305, . (16/02012-4, 17/26872-5, 15/22944-6)

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