Inhibition by the JAK/STAT pathway of IFNγ- and LPS-stimulated nitric oxide synthase induction in vascular smooth muscle cells

Inducible nitric oxide synthase (iNOS) is induced in many cell types by cytokines and lipopolysaccharide (LPS). Cytokine signal transduction is believed to be mediated primarily through the JAK/STAT pathway. We therefore examined the effects of a JAK2-specific inhibitor, an antisense oligonucleotide to JAK2, and electroporation of neutralizing anti-STAT1 and anti-STAT3 antibodies on IFN gamma- and LPS-stimulated induction of iNOS in vascular smooth muscle cells. Unexpectedly, we found that the JAK/STAT pathway suppresses IFN gamma- and LPS-stimulated iNOS induction in these cells. In contrast, the JAK/STAT pathway appears to have a positive role in iNOS induction in RAW 264.7 macrophages. (C) 1998 Academic Press.