Differential cellular signaling in thyroxine-mediated proliferation of normal and tumor T lymphocytes

M.L. BARREIRO ARCOS, G. GORELIK, A.J. KLECHA AND G. CREMASCHI

Venecia, Italia

Congreso; 7 Th International Congress of Neuroimmunology; 2004

International Society of Neuroimmunology (ISNI)

Thyroid hormone regulation of immune responses was demostrated. In addition, differential expression of protein kinase C (PKC) isoenzymes and high nitric oxide synthase (NOS) activity were described on tumor respect to normal T lymphocyte. L-Thyroxine (T4)-mediated actions on both enzymatic activities, related to T lymphocyte and BW 5147 T lymphoma cell proliferation were studied. Thyroid hormones increase tumor, but not normal, cell proliferation and potentiated mitogen-stimulation of T lymphocytes as measured by tritiated-thymidine incorporation. Twenty-four-hour incubation with T4 induced a rise in total and membrane-associated PKC activities, as measured by [gamma-32P]-ATPphosphorylation of PKC specific substrate, on both cell types. In addition, T4 potentiated mitogen-induced PKC translocation in normal T lymphocytes and lead to a rapid and transient effect on tumor cells. T4 increased atypical PKC zeta expression on BW 5147, but classical PKC isoenzymes on mitogen-stimulated normal T cells by immunoblotting analysis. Additionally, T4 augmented NOS activity, measured by production of [U-14C]-citrulline from [U-14C]-arginine, only on tumor cells. These re4sults show, for the first time, differential intracellular signals involved in T4 modulation of lymphocyte biology.