PKC theta cooperates with PKC alpha in alloimmune responses of T cells in vivo.

The physiological roles of PKC alpha and PKC theta were defined in T cell immune functions downstream of the antigen receptor. To investigate the hypothesis that both PKC isotypes may have overlapping functions, we generated mice lacking both genes. We find that PKC alpha(-/-)/theta(-/-) animals have additive T cell response defects in comparison to animals carrying single mutations in these genes.

In vivo characterization of the novel imidazopyridine BYK191023 [2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine], a potent and highly selective inhibitor of inducible nitric-oxide synthase.

Excessive release of nitric oxide from inducible nitric-oxide synthase (iNOS) has been postulated to contribute to pathology in a number of inflammatory diseases. We recently identified imidazopyridine derivatives as a novel class of potent nitricoxide synthase inhibitors with high selectivity for the inducible isoform. In the present study, we tested the in vivo potency of BYK191023 [2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo-[4,5-b]pyridine], a selected member of this inhibitor class, in three different rat models of lipopolysaccharide-induced systemic inflammation.

PKCdelta is involved in signal attenuation in CD3+ T cells.

PKCdelta has been implicated in the signalling events after engagement of the antigen specific receptor on B cells and the Fc-epsilon receptor on mast cells. Employing our recently established PKCdelta null mice , we here investigate the physiological function of PKCdelta in CD3+ T cells. As result, administration of anti-CD3 antibodies in vivo induced markedly increased blood plasma IL-2 levels (but not IL-4, IFN-gamma, TNF-alpha and IL-6 levels) in the PKCdelta null mice, when compared to wild-type sibling controls.