EVALUATION OF ANTI-IL-17 IN THE MODULATION OF INFLAMMATION, REMODELING AND SIGNALING PATHWAYS IN MODEL OF ASTHMA-COPD OVERLAP.

• Grant number: 21/13630-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2022
• Effective date (End): February 19, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Miguel Cantadori Barbeiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

IL-17 is involved in the recruitment of eosinophils and neutrophils. Despite its inhibition being able to modulate inflammatory and functional responses in asthma and COPD, there are no studies addressing these aspects in ACO. Currently, treatments with monoclonal antibodies are important for patients with difficult-to-control asthma. Therefore, the study of IL-17 in patients with ACO becomes essential, as these patients respond poorly to conventional treatments, thus requiring studies for a therapeutic alternative. In the present study, the effects of anti-IL-17 on the modulation of inflammation, remodeling and signaling pathways in the airway and lung parenchyma will be evaluated in an experimental model of ACO, evaluating:A) the recruitment of anti and pro-inflammatory cytokines (IL-10, IL-4, IL-1b, IL-17)B) extracellular matrix elements: collagen fibers type I, III, V and TIMP-1C) response of signaling pathways (ROCK-1, ROCK-2, NFkb)Two sensitization protocols will be used, one for induction of lung inflammation by ovalbumin and the other for induction of lung injury induced by elastase, both will last 28 days. 24 hours after the end of the experimental protocols, the animals will be anesthetized and exsanguinated and the lungs will be removed en bloc with the heart for morphometric studies and histological/histochemical analyzes for the numbers of IL-10, IL-4, IL-1b, IL-17, collagen types I, III, V and TIMP-1, ROCK-1, ROCK-2 and NFkb.