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Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by Naphthoquinone (vitamin K) compounds

1995; Elsevier BV; Volume: 7; Issue: 3 Linguagem: Inglês

10.1006/cyto.1995.0034

1096-0023

Krisanavane Reddi, Brian E. Henderson, S Meghji, Michael A. Wilson, Stephen Poole, Colin Hopper, M. Harris, Stephen Hodges,

Bioactive Compounds and Antitumor Agents

Naphthoquinnone vitamins (vitamins K) are widely recognized for their role in the γ-carboxylation of specific glutamyl residues in coagulation, anti-coagulation and extra-hepatic proteins. Recently, however, there have been reports that these compounds can exert actions other than those normally associated with protein γ-carboxylation. These observations suggest that naphthoquinones may have effects on the production of inflammatory mediators including cytokines. Fibroblasts are now recognized as a rich source of cytokines and we have examined the effect of various naphthoquinones on the production of interleukin 6 (IL-6) by lipopolysaccharide-stimulated human gingival fibroblasts. Compounds examined in this study include: phylloquinone (K1), menaquinone-4 (K2), menadione (K3), 2,3-dimethoxy-1,4-naphthoquinone (DMK) and a synthetic product of vitamin K catabolism, 2-methyl, 3-(2′methyl)-hexanoic acid-1,4-naphthoquinone (KCAT). All of these compounds are capable of inhibiting IL-6 production with a rank order of potency: KCAT>K3>DMK>K2>K1. The most potent compound, KCAT, inhibited IL-6 with an IC50of 3×10−7M. The mechanism of action of these naphthoquinones on fibroblast IL-6 production is unknown. Given that K3 and KCAT are inactive in the γ-carboxylation reaction, we suggest that this activity is not essential for the inhibition of IL-6 production and that activity may be related to the redox capacity of these naphthoquinones.