Thyroxine stimulates normal and tumor T lymphocyte proliferation via different pathways involving protein quinase C isoenzymes and nitric oxide synthase.

BARREIRO ARCOS ML, GORELIK G, KLECHA A AND CREMASCHI G.

Tandil, Argentina

Congreso; XXXIV Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2002

Sociedad Argentina de Farmacología Experimental

Previously, we have shown a different protein kinase C (PKC) isoform pattern and a high activity of nitric oxide synthase (NOS) in a T lymphoma cell line BW5147 (BW) respect to normal T cells. Regulation of immune responses by thyroid hormones was demonstrated.  In this work, the effects of thyroxine (T4) upon normal and tumor lymphocyte activities were studied. T4 stimulated both, mitogen-activated normal and tumor T cells proliferation in a doses-dependent manner, measured by [3H]-thymidine incorporation.  After 24-72 hs of culture in the presence of T4 a rise in total PKC content accompanied by an increased membrane associated PKC activity was observed on both cell types. This was accompanied by an increase in the atypical, Ca2+- independent PKCz or in the classical PKC isoforms on BW and mitogen-stimulated normal T cells, respectively, as assessed by Western blot. T4 augmented NOS activity in BW, but not in mitogen-stimulated normal T cells, as determined by [14C]-citrulline production from [14C]-arginine. We conclude that T4 modulates proliferation of both normal and tumor T lymphocyte through PKC activity, but involving different PKC isoenzymes and stimulating NOS activity only on BW cells. This points to a differential effect of T4 on normal and tumor T cell activation.