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Action of triiodothyronine (T3) in macrophages differentiation: activation of the classical or alternative pathway

Grant number: 13/24574-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2014
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Celia Regina Nogueira
Grantee:Bruna Moretto Rodrigues
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Has already been confirmed the existence of a bidirectional relationship between the endocrine and immune systems, modulated by signaling molecules as hormones and cytokines. The thyroid hormones T3 and T4 acts on immune cells functions and the immune system indirectly influences the synthesis of those hormones, through cytokines as IL-1, IL-6 and TNF-±. Has been reported the presence of T3 in several immune cells such as macrophages, important effectors cells of the immune responses involved in antigen presentation, microbicidal and tumoricidal activity and regulatory functions. The thyroid hormones modulate the enzyme's activities and hydrogen peroxide production in macrophages, that may influences the innate and adaptive immunity of those cells. The T4 could exert an anti-inflammatory role on them. Molecules like lipopolysaccharide and some cytokines, such as TNF-a, IL-1 and IFN-g, induces the activation of the classical pathway of macrophages (M1) stimulating the production of several pro-inflammatory mediators and increases the iNOS and oxide nitric (NO) expression. Th2 cytokines and glucocorticoids, in turn, induces the activation of the alternatively pathway of macrophages (M2) increasing the arginase-1 activity and expression receptors of scavengers and antagonists IL-1. The inflammatory and antifibrotic effects of Th1 response are markedly dependents on iNOS. Stimulated macrophages with Th2 cytokines produce proline, an important precursor of collagen, on the strict control of arginase. The project aims to evaluate the ability of thyroid hormones (T3 and T4) to modulate the differentiation of M1 and M2 macrophages, thereunto, will evaluate the NO produce, expression of cytokines TNF-±, IL-6, IL-10 and TGF-² (ELISA) and gene expression of iNOS, arginase, FIZZ-1 and YM1 induced in activated macrophages (PCR in real time)