Different mitogen-mediated beta-adrenergic receptor modulation in murine T lymphocytes depending on thyroid status.

A. J. KLECHA; M. L. BARREIRO*; A.M. GENARO; G. GORELIK; D.M. SILBERMAN; R. CARO; G. A. CREMASCHI

NEUROIMMUNOMODULATION.

Karger AG

Lugar: Basel; Año: 2005 vol. 12 p. 92 - 99

1021-7401

Objective: The aim of this work was to analyze ß-adrenergic receptor (ßAR) regulation of T-lymphocyte proliferation in mice according to different thyroid hormone statuses. Methods: T cells from eu-, hypo- (by propylthiouracil treatment) and hyperthyroid (by thyroxine, T4 administration) mice were purified and specific radioligand binding assays were performed. The effects of the ß-agonist isoproterenol (ISO) on intracellular levels of cyclic AMP (cAMP) were determined. Mitogen-induced T-cell proliferation was measured by [3H]-thymidine incorporation. Finally, protein kinase C (PKC) activity in cytosol and membrane fractions were determined using radiolabelled enzymatic substrates. Results: A decrease or a non-significant increase in ßAR number was found on T lymphocytes from hypo- and hyperthyroid mice compared to euthyroid controls. ISO stimulation of cAMP levels was lower in hypothyroid and higher in hyperthyroid  T lymphocytes compared to controls. T-selective mitogen-induced proliferation was increased in T4-treated animals, but decreased in hypothyroid mice. During the peak of proliferation, downregulation of ßAR was observed in all animals. However, a higher or a lower decrease was observed in hyper- and hypothyroid T cells, respectively. In parallel, a higher translocation of PKC activity was observed in hyperthyroid cells, and a lower one was found in hypothyroid lymphocytes with respect to controls. Conclusions: These results indicate that intracellular signals triggered by mitogen activation, namely PKC, would be related to differential ßAR down-regulation in T lymphocytes depending on the thyroid hormone status, contributing to the distinct proliferative responses found in hypo- or hyperthyroidism comparedto the euthyroid state.