Role of anexin A1 and NLRP3 inflamassoma in inflammatory skin diseases: study on patients and model biopsies in vitro

• Grant number: 21/03847-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2021
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Rebeca Donizete Correia da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Using clinical criteria, Psoriasis and Atopic Dermatitis are clearly defined skin diseases. However, the pathogenesis of both diseases has many overlaps and similarities related to thea ctivation of the immune response and caused tissue changes. Thus, the study of the molecular and cellular mechanisms involved in this inflammatory cascade will contribute to the development of more effective therapies for chronic inflammation of the skin. In this context, we highlight the protein annexin A1 (ANXA1) and the inflammasome NLRP3, importante mediators related to the regulation of the inflammatory response, such as activation of leukocytes and release of cytokines, whose roles in skin inflammation are not well defined. Thus, we will evaluate the expression pattern of ANXA1 and NLRP3 in Psoriasis (Ps) Andatopic Dermatitis (AD). In addition, we will evaluate in vitro the effect of the administration of ANXA1 mimetic peptide, Ac2-26, on human keratinocytes, HaCaT lineage, stimulated by IL-17or IL-4. Skin biopsies with Ps and AD will be used (n = 10 for each). For the control group, we will use biopsies of clinically normal skin margins removed along with skin tumors (n = 10). For in vitro studies, HaCaT cells will be treated with Ac2-26 and after 15 minutes stimulated byIL-17 or IL-4. Some cells will receive, 15 minutes before stimulation with cytokines, Boc2 orWRW4, antagonists of ANXA1 receptors - FPR1 and FPR2, respectively, followed by Ac2-26. Several technical approaches will be used: immunohistochemistry, immunofluorescence, western blotting, ELISA, cell viability assay, bioinformatics analysis, etc. The results will contribute to a better understanding of the biological actions and molecular mechanisms that involve ANXA1/NLRP3 in skin inflammations. (AU)