Regulation of inducible and neuronal nitric oxide synthase gene expression by interferon-gamma and VIP

Abstract

The studies examined the regulation of inducible and neuronal nitric oxide synthases (iNOS and nNOS, respectively) in the rat brain, stomach, rectum, and spleen. Relative expression of iNOS and nNOS mRNAs was quantified by the sensitive method of polymerase amplification reactions. The NOS proteins were determined by Western blot, using specific antibodies. Highest levels of nNOS and iNOS mRNAs were expressed in the rat brain and spleen, respectively. Furthermore, both nNOS and iNOS were expressed in the stomach and rectum. Interestingly, treatment of tissues with lipopolysaccharides or cytokine interferon-gamma (IFN-gamma) induced the expression of iNOS and decreased that of nNOS, representing a shift from one isoform to the other. When the tissues were treated with IFN-gamma followed by vasoactive intestinal polypeptide (VIP), the induction of iNOS was reduced by VIP. The changes in iNOS and nNOS expression at the transcriptional level corresponded to those at the translational level. The data suggest a regulatory role of IFN-gamma and VIP in the expression iNOS and nNOS and a counterregulation of iNOS and nNOS in rat tissues.