Participation of nitric oxide synthase (NOS) and atypical protein kinase C (PKC) zeta in thyroid hormone-mediated apoptosis of murine T lymphocytes.

CREMASCHI GA; KLECHA AJ; VERCELLI C; FRANCHI AM; GENARO AM; BARREIRO ARCOS ML

Miami, USA

Congreso; 94th Annual Meeting of The American Association of Immunologists; 2007

The American Association of Immunologists

TH regulate immune responses and are able to influence proliferation and differentiation in several cell types, but their direct actions on lymphocytes have not been elucidated. We have demonstrated that short time culture (up to 72 h) of quiescent BW5147 (BW) T cells in the presence of TH induced cell division. Here prolonged actions of TH on BW cells and the intracellular signals involved were studied. After 5 days of culture HT inhibited BW growth inducing apoptosis, as shown by Hoescht staining and DNA ladder assay. These effects were accompanied by an increase in NOS activity measured by [14C]-citrulline formation. Also, an increase in iNOS and a decrease in the PKC zeta isoform, both at the protein (by western blot analysis) and mRNA levels (by RT-PCR evaluation) were seen An increase in reactive oxygen species (determined by conversion of dichlorofluorescin-diacetate to the fluorescent DCF) was found. Additionally, TH induced an increment in protein nitrosylation. These results show that prolonged HT exposition lead to an exacerbate increase in iNOS activity, that would in turn result in PKC zeta decrease, probably through protein nitrosylation. These intracellular signals would trigger apoptotic mechanisms involved in TH regulation of lymphocyte activity.