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

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, J744A.1. By DSG treatment NO2- accumula tion in the medium was blocked, and cellular iNOS protein level decreased a s shown by Western blotting. DSG didn't have any direct effect on iNOS activity. DSG was not used as a s ubstrate of NOS in in vitro enzyme systems, and it was too weak an inhibito r 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 immu nosuppressive activity.