Stimulation of normal and tumor lymphocyte proliferation by thyroid hormones. Differential roles for protein quinase C isoenzymes and nitric oxide synthase.

MARÍA LAURA BARREIRO ARCOS, GABRIELA GORELIK, ALICIA KLECHA, GRACIELA CREMASCHI.

Bristol, Inglaterra

Congreso; V International Congress of Neuroendocrinology; 2002

Society of Neuroendocrinology

Previously, we have shown a different PKC isoform profile and a high activity of NOS in a T lymphoma cell line BW5147 (BW) respect to normal T lymphocytes. Also regulation of the immune response by thyroid hormones was demonstrated.  In this work the effects of thyroid hormones upon normal and tumoral lymphocyte activity was studied. TH stimulated both mitogen-activated normal T lymphocytes and tumor T lymphocytes proliferation in a concentration-dependent manner as was measured by [3H]-timidine incorporation.   After 24-72 hs of culture in the presence of thyroxine (T4) an increment in total PKC content from both cell types was observed. Moreover, this was accompanied by an increment of membrane associated PKC activity. However T4 was unable to modifying PKC isoenzyme profile, measured by Western blot analysis on both normal-activated and tumor T cells, but it increased the atypical Ca-independent PKCz isoform expression in BW cells. On the other hand, T4 increased NOS activity in BW lymphocytes but not in resting or mitogen-stimulated NTL, as determined by production of [14C]-citrulline from [14C]-arginine. We conclude that TH and specially T4, modulate normal and tumoral lymphocyte activity probably through increasing PKC activity but without modifying PKC isoenzymes distribution.  Nevertheless the increment in PKCz isoenzyme expression together with NOS activity augment in tumoral T lymphocytes point to a differential effect of thyroid hormones on normal and tumoral T cells activity.