Role of Annexin-A1 in experimental model of atopic dermatitis in mice

Abstract

Atopic Dermatitis (AD), also known as atopic eczema, is the most common chronic skin inflammation, with multifactorial etiology, characterized by the production of IgE and Th2 cytokine profile (IL,4 and IL-13). Treatments for AD include emollients, topical corticosteroids, phototherapy, and immunosuppressive drugs, but their adverse effects stimulate search for new therapeutic strategies. Thus, we highlight the annexin A1 (ANXA1), a protein that has a potent anti-inflammatory action, which can be activated by its interaction with formyl peptide receptor (Fpr2). However, the role of ANXA1 and its relationship with Fpr2 on normal and inflamed skin has been little explored. Thus, we will analyze the effects caused by the absence of endogenous ANXA1 in allergic inflammatory response on skin and Fpr2 expression in an experimental murine model of AD. Wild type and ANXA1 knockout C57BL/6 male mice will be immunized with a subcutaneous injection of ovalbumin (OVA; 5 µg) in the days 0 and 7. After immunization, mice will be challenged with 250 µg OVA diluted in 50µl Johnson's Baby ® oil, in the days 11, 14 to 18 and 21 to 24. After 24 hours of the last OVA challenge, or just oil (sham), mice will be anaesthetized to blood collection, and then euthanized by cervical dislocation to collect skin for further analysis. Studies will be conducted through: dosage of IgE anti-OVA by ELISA in blood; histological analysis and quantification of mast cells and eosinophils in skin; western blotting and immunohistochemistry to detect eosinophils and mast cells mediators, extracellular signal-regulated kinase (ERK) and Frp2 expression in skin. The results will contribute to a better understanding of the cellular and molecular mechanisms involved in the biological action of ANXA1 in allergy, as well as potential therapeutic targets for inflammatory conditions of the skin. (AU)