Original Article

Dithiolane analogs of lignans inhibit interferon-gamma and lipopolysaccharide-induced nitric oxide production in macrophages

Authors: Isa M Hussaini, Yi-Hua Zhang, Jeff J Lysiak, Tsung Y Shen


To investigate the effect of a group of novel synthetic dithiolane analogs of lignans and a well characterized platelet-activating factor (PAF) receptor antagonist, L659,989 on PAF-receptor binding, IFN-gamma- and lipopolysaccharide (LPS)-induced NO production, and steady-state inducible nitric-oxide synthase (iNOS) mRNA expression.
PAF-receptor binding study was performed by displacement of 3H-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 Northern blot analysis.
The dithiolane analogs inhibited the production of NO, decreased iNOS mRNA expression and antagonized PAF-receptor binding. L659,989 had no effect on NO production and iNOS mRNA expression. Among the compounds tested, there was no simple correlation between their PAF-receptor antagonistic and iNOS inhibitory activities.
The dithiolane analogs are a new synthetic chemical class of iNOS expression regulators with dual biologic functions: inhibiting iNOS induction and blocking PAF-receptor."

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