INTERLEUKIN-6 PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED HUMAN FIBROBLASTS IS POTENTLY INHIBITED BY NAPHTHOQUINONE (VITAMIN-K) COMPOUNDS
INTERLEUKIN-6 PRODUCTION BY LIPOPOLYSACCHARIDE-STIMULATED HUMAN FIBROBLASTS IS POTENTLY INHIBITED BY NAPHTHOQUINONE (VITAMIN-K) COMPOUNDS
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DOI：
10.1006/cyto.1995.0034
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发表时间：
1995-04-01
期刊：
影响因子：
3.8
通讯作者：
HODGES, SJ
中科院分区：
文献类型：
--
作者：
REDDI, K;HENDERSON, B;HODGES, SJ
萘醌维生素（维生素K）因其在凝血、抗凝血和肝外蛋白中特定谷氨酰残基γ -羧基化中的作用而被广泛认可，然而，最近有报道称，这些化合物可以发挥与蛋白质γ -羧基化不同的作用。这些观察结果表明萘醌类。可能对包括细胞因子在内的炎症介质的产生有影响，成纤维细胞现在被认为是细胞因子的丰富来源，我们已经研究了各种萘醌对脂多糖刺激的人牙龈成纤维细胞产生白细胞介素6 （IL-6）的影响。本研究检测的化合物包括：叶绿醌（K1）、甲基萘醌-4 （K2）、甲基萘醌（K3）、2,3-二甲氧基-1,4-萘醌（DMK）和维生素K分解代谢的合成产物z -甲基、3-（2'甲基）-己酸-1,4-萘醌（KCAT），所有这些化合物都能抑制IL-6的产生，其效价依次为：KCAT>K3>DMK>K2>K1，最有效的化合物KCAT抑制IL-6的产生，IC50为3 × 10(-7)M，这些萘醌类化合物对成纤维细胞IL-6产生的作用机制尚不清楚，鉴于K3和KCAT在γ -羧基化反应中不活跃，我们认为这种活性不是抑制IL-6产生所必需的，这种活性可能与这些萘醌类化合物的氧化还原能力有关。
Naphthoquinone vitamins (vitamins K) are widely recognized for their role in the gamma-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 gamma-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, Z-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 production with an IC50 of 3x10(-7)M, The mechanism of action of these naphthoquinones on fibroblast IL-6 production is unknown, Given that K3 and KCAT are inactive in the gamma-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.