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

KLECHA AJ, BARREIRO ARCOS ML, GENARO AM, GORELIK G, SILBERMAN DM, CARO R, CREMASCHI GA.

NEUROIMMUNOMODULATION.

S. Karger, Basel

Año: 2005 vol. 12 p. 92 - 99

1021-7401

OBJECTIVE: The aim of this work was to analyze beta-adrenergic receptor (betaAR) 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 beta-agonist isoproterenol (ISO) on intracellular levels of cyclic AMP (cAMP) were determined. Mitogen-induced T-cell proliferation was measured by [(3)H]-thymidine incorporation. Finally, protein kinase C (PKC) activity in cytosol and membrane fractions were determined using radiolabelled enzymatic substrates. RESULTS: Adecrease or a non-significant increase in betaAR 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 betaAR 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 betaAR downregulation in T lymphocytes depending on the thyroid hormone status, contributing to the distinct proliferative responses found in hypo- or hyperthyroidism compared to the euthyroid state.