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The role of SOCS and STATs proteins on the differentiation of cells CD4 + naive in the chronic obstructive pulmonary disease (COPD) development in both smokers patients and experimental model exposure to cigarette smoke

Grant number: 16/17817-8
Support type:Regular Research Grants
Duration: July 01, 2017 - June 30, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernanda Degobbi Tenorio Quirino dos Santos Lopes
Grantee:Fernanda Degobbi Tenorio Quirino dos Santos Lopes
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Carla Máximo Prado ; Elnara Marcia Negri ; Rodolfo de Paula Vieira

Abstract

In a previous study we demonstrated that COPD smokers showed decreased regulatory T cells density (Treg) with a decrease for their immunosuppressant interleukins TGF beta and IL-10 compared to smokers without obstruction. Also, it was also detected increased positive cells density for IL-17, featuring a Th17 response profile in these individuals. Considering the role of intracellular proteins STAT (the English "Activator of Transcription Protein") and SOCS (English "Suppressor Of Cytokine Signaling") in the differentiation of CD4 + cells naive in its subtypes Objective: We intend, in this study, to evaluate the mechanisms involved in the differentiation of CD4 + naive cells to Th17, and Treg and Th1 subtypes considering the role of STAT and SOCS proteins in COPD. We will perform assessments in tissues and plasma samples from patients and in experimental model, which will also allow us to evaluate how much the experimental model reflects the observed in humans Methods: Protocol 1: We will study patients undergoing pulmonary resection for primary metastatic tumor, divided into two groups: Non Obstructive smokers and Obstructive Smokers. Protocol 2: For the induction of pulmonary emphysema, mice will be exposed to cigarette smoke for 3 and 6 months, and the control animals remain exposed to ambient air. For both protocols, we will evaluate the interleukins -6, -10, - 17, and TGF-² and IFN-³ in lung samples and blood plasma to check systemic and local response. In the lungs we will assess the density of positive cells for IL-17 (Th17 profile), IFN-³ (Th1 profile) and Treg, STAT 3, 5 total and phosphorylated and SOCS 1 and 3. We will quantify by immunoblotting STAT 3, 5 total and phosphorylated and SOCS 1 and 3 . We will evaluate the gene expression for STAT 3, 5 and SOCS1 and 3 in tissue and plasma of individuals of the Protocol 1 by real-time PCR . (AU)