Thyroid hormone-mediated modulation of T cell activation through the regulation of the alpha isoform of their receptor (TRalfa1).

BARREIRO ARCOS ML; STERLE H A; PAULAZO MA; VALLI E; KLECHA AJ; FARIAS RN; CREMASCHI GA

Foz do Iguazú

Congreso; XXXIX Reunión Anual de la Sociedad Brasilera de Bioquímica y Biología Molecular.; 2010

Sociedad Brasilera de Bioquímica y Biología Molecular (SBBq).

Thyroid hormones (THs) exert actions in cellular growth and differentiation of cells by inducing non-genomic and genomic mechanisms, and they are also able to regulate the immune response. The physiological mechanisms involved in TH actions on lymphocytes are not known. In this work we have analyzed the signaling pathways involved in the proliferative effects of TH on a T cell line, namely BW 5147. Free THs (T3 and T4) and their agarose-coupled analogs (T3-ag and T4-ag) stimulated T cell proliferation, although the latter to a lesser extent. Both, free THs as well as T3-and T4-ag, induced PKCzeta activation upstream of NF-kB and ERK pathways, as treatment with PKCzeta pseudosubstrate blocked the translocation of NF-kB to the  cell nucleus and the phosphorylation of ERK. Free and agarose-coupled THs were able to induce non-genomic activation of NOS and to increase the protein and mRNA levels of both the inducible isoform of NOS (iNOS) and the a isoform of their receptor (TRalpha1), which subsequently returned to basal levels, thus indicating the existence of self-regulatory mechanisms induced by THs. These results suggest that genomic and genomic effects of TH regulate T lymphocyte activity, involving the activation of kinases and NF-kB, regulating the iNOS expression and the hormone receptor itself.