Involvement of the annexin A1-Fpr anti-inflammatory system in the ocular allergy

Author(s)

Marmorato, Mariana Prado ^[1] ; Gimenes, Alexandre Dantas ^[1] ; Costa Andrade, Frans Eberth ^[1] ; Oliani, Sonia Maria ^[2] ; Gil, Cristiane Damas ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP, Dept Morfol & Genet, Rua Botucatu 740, Ed Lemos Torres 3 Andar, BR-04023900 Sao Paulo, SP - Brazil

^[2] Univ Estadual Paulista, UNESP, Inst Biociencias Letras & Ciencias Exatas IBILCE, Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 842, p. 298-305, JAN 5 2019.
• Web of Science Citations: 2

Abstract

Annexin A1 (ANXA1)-formyl peptide receptor (Fpr) system is potent effective mediators in the control of the inflammatory response. In this study, we evaluate the potential involvement of the Fpr family in the protective effect of the mimetic peptide of ANXA1 (ANXA1(2)(-)(26)) using an experimental allergic conjunctivitis (AC) model in mice. Ovalbumin (OVA)/Alum-immunized wild-type (WT) and ANXA1-null (ANXA1(-/-)) Balb/c mice (days 0 and 7) were challenged by eye drops containing OVA on days 14-16, and two groups received ANXA1(2)(-)(26) alone or with Fpr antagonist Boc2 intraperitoneally during challenged days. As expected, plasma IgE anti-OVA levels increased significantly in the OVA-immunized WT and ANXA1(-/-) mice, supporting the efficacy of AC model. AC increased Fpr1 and Fpr2 levels in the conjunctiva and the lack of endogenous ANXA1 exacerbated Fpr2 expression only. In contrast, administering ANXA1(2)(-)(26) in the WT mice diminished Fpr2 levels in the conjunctiva, and the effect was reverted by Boc2. Ultrastructural analysis showed the co-localization of Fpr2 and ANXA1 in the plasma membrane of mast cells (MCs), eosinophils and neutrophils, supporting this system as being operative in the AC. Boc2 abrogated the ANXA1(2)(-)(26) effect by increasing the MC degranulation and the eosinophil influx in the conjunctiva, and these findings were supported by peroxidase eosinophil, eotaxin and MC protease levels. Additionally, the ANXA1(2)(-)(26)-Fpr system in the AC was associated with the activation of ERK and JNK. Collectively, the data provided in vivo supports the anti-allergic effects of the ANXA1-Fpr system and may serve as a therapeutic target in this ocular disorder. (AU)

• FAPESP's process: 16/02012-4 - Evaluation of the immunomodulatory activity of annexin A1 protein in the regulation of inflammatory disorders of the gastrointestinal system: studies in vivo and in vitro experimental models
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/26872-5 - Study of anti-inflammatory and proinflammatory proteins as possible therapeutic targets in experimental models of neuroinflammation and cutaneous inflammation
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/22944-6 - Role of formyl peptide receptors and mimetic peptide of Annexin A1 in the ocular allergy
• Grantee: Mariana Prado Marmorato
• Support Opportunities: Scholarships in Brazil - Scientific Initiation