Impaired response to interferom-γin activated macrophages due to tyrosine nitration of STAT1 by endogenous nitrc oxide

摘要

Indicible NO synthase(iNOS)expression and activity were measured in the mouse macrophage cell line J774 after exposure to bacterial lipopolysaccaride(LPS)with or without interferon-γ)IFN-γ). Inhibition of NOS activity by concomitant N~G-monomethyl-L-arginine(L-NMMA)treatment Further increased iNOS protein levels, with a substantial increase in iNOS half-life. Western blotting and ELISA demonstrated that several cell proteins were tyrosine-nitrated when ONOS activity was high. Rapid IFN-γ-induced phosphorylation of STAT1 was reduced by about 40/100 when cells were Pretreated to induce iNOS, unless L-NMMA was present during the pretreatment period.