REGULATION OF INDUCIBLE AND NEURONAL NITRIC-OXIDE SYNTHASE GENE-EXPRESSION BY INTERFERON-GAMMA AND VIP

The studies examined the regulation of inducible and neuronal nitric o xide synthases (iNOS and nNOS, respectively) in the rat brain, stomach , rectum, and spleen. Relative expression of iNOS and nNOS mRNAs was q uantified by the sensitive method of polymerase amplification reaction s. The NOS proteins were determined by Western blot, using specific an tibodies. Highest levels of nNOS and iNOS mRNAs were expressed in the rat brain and spleen, respectively. Furthermore, both nNOS and iNOS we re expressed in the stomach and rectum. Interestingly, treatment of ti ssues with lipopolysaccharides or cytokine interferon-gamma (IFN-gamma ) induced the expression of iNOS and decreased that of nNOS, represent ing a shift from one isoform to the other. When the tissues were treat ed with IFN-gamma followed by vasoactive intestinal polypeptide (VIP), the induction of iNOS was reduced by VIP. The changes in iNOS and nNO S 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 iNO S and nNOS in rat tissues.