Inhibition of nitric oxide synthase induction by 15-deoxyspergualin in a cultured macrophage cell line, J774A.1 [correction of J744A.1] activated with IFN-gamma and LPS.

Abstract

Immunosuppressant 15-deoxyspergualin (DSG) inhibited induction of inducible nitric oxide synthase (iNOS) following stimulation with IFN-gamma and LPS in a cultured macrophage cell line, J774A.1 [corrected]. By DSG treatment NO2- accumulation in the medium was blocked, and cellular iNOS protein level decreased as shown by Western blotting. DSG didn't have any direct effect on iNOS activity. DSG was not used as a substrate of NOS in in vitro enzyme systems, and it was too weak an inhibitor of iNOS and cNOS to cause the inhibition of accumulation of NO2-. DSG did not scavenge NO spontaneously generated from NOR. Structure-activity relationships of analogs and decomposed elements showed that there is correlation between the inhibition of iNOS induction and immunosuppressive activity.