Im. Hussaini et al., Dithiolane analogs of lignans inhibit interferon-gamma and lipopolysaccharide-induced nitric oxide production in macrophages, ACT PHAR SI, 21(10), 2000, pp. 897-904
AIM: To investigate the effect of a group of novel synthetic dithiolane ana
logs of lignans and a well characterized platelet-activating factor (PAF) r
eceptor antagonist, L659,989 on PAF-receptor binding, IFN-gamma- and lipopo
lysaccharide (LPS)-induced NO production, and steady-state inducible nitric
-oxide synthase (iNOS) mRNA expression. METHODS: PAF-receptor binding study
was performed by displacement of H-3-PAF from rabbit platelet membrane; NO
production was quantitated by measuring the NO oxidation product, nitrite,
in conditioned culture medium; expression of iNOS mRNA was assessed by Nor
thern blot analysis. RESULTS: The dithiolane analogs inhibited the producti
on of NO,; decreased iNOS mRNA expression and antagonized PAF-receptor bind
ing. L659,989 had no effect on NO production and iNOS mRNA expression. Amon
g the compounds tested, there was no simple correlation between their PAF-r
eceptor antagonistic and iNOS inhibitory activities. CONCLUSION: The dithio
lane analogs are a new synthetic chemical class of iNOS expression regulato
rs with dual biologic functions: inhibiting iNOS induction and blocking PAF
-receptor.