Cyclic AMP regulate adenovirus mediated inducible nitric oxide synthase expression and CMV promoter activity in cultured hepatocytes

We examined effects of cyclic AMP on adenovirus mediated inducible nitric oxide synthase expression in primary rat hepatocytes. In AdCMV-hiNOS infected hepatocytes, dbcAMP at a concentration of 1-100 muM inhibited nitrite and nitrate accumulation, iNOS protein and iNOS mRNA expression. At a concentration of 1-5 mM, dbcAMP increased iNOS activity and expression. Both the inhibitory and stimulatory effects of cAMP on adenovirus mediated iNOS expression were dose dependent. This dual effect of cAMP on iNOS activity and expression can be accounted by its effect on CMV promoter activity since dbcAMP significantly inhibited CMV promoter activity in hepatocytes at low concentration and induced it at high concentration. We concluded that dbcAMP can regulate adenovirus-mediated human iNOS expression in primary hepatocytes by the mechanisms regulating the CMV promoter used in the adenovirus vector. (C) 2003 Elsevier Inc. All rights reserved.