C. Nosaka et al., Inhibition of nitric oxide synthase induction by 15-deoxyspergualin in a cultured macrophage cell line, J744A.1 activated with IFN-gamma and LPS, J ANTIBIOT, 52(3), 1999, pp. 297-304
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.