Evaluation of the effects arising from the treatment with cryptotansinone on the imbalance of Th17 and Treg responses in an experimental model of chronic obstructive pulmonary disease

• Grant number: 23/06001-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Franciele Jesus Lima
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by slow and progressive limitation ofairflow that is not fully reversible, with chronic bronchitis and pulmonary emphysema being theits main manifestations. Smoking is considered the main risk factor fordevelopment of the disease, providing a chronic inflammatory process mediated by immunityinnate and adaptive. In previous studies developed by our group, we demonstrated that the progressionof COPD was associated with decreased control of the inflammatory response mediated by T cellsregulators (Treg) via release of interleukin (IL) -10 and consequent increase in responseinflammatory response mediated by T helper (Th) 17 cells via IL-17 release. Furthermore, we demonstrate theimportance of intracellular STAT proteins in this response from the beginning of the development ofillness. Some inhibitors of these proteins have demonstrated an important role in the control ofinflammatory process in different diseases, such as cryptotansinone, a specific inhibitor forSTAT3, involved in the differentiation of Th17 cells, thus providing control of the processinflammatory. Objective: To evaluate the effects of treatment with cryptotansinone in the differentiation ofTh17 and Treg responses in an experimental model of exposure to cigarette smoke. Methods: For theinduction of pulmonary emphysema, C57BL/6 mice will be exposed to cigarette smoke (twice aday / 30 minutes / 5 days a week / for 6 months), and the control animals will remain exposed tofiltered air. The animals will receive cryptotansinone treatment from the fourth month of the protocol (2times a week, intraperitoneally, 20 mg/Kg). We will carry out the evaluation of respiratory mechanicsto obtain functional parameters and histological analyzes to evaluate the enlargement of theair spaces. We will use the ELISA technique to quantify IL-6, IL-10, IL-17 and TGF-². For theimmunoblotting technique, we will perform a quantitative analysis of total and phosphorylated STAT 3 and 5. PerRT-PCR will do STAT 3, 5 and RORyT gene evaluation.