Novoselova Elena G, Lunin Sergey M, Novoselova Tatyana V, Khrenov Maxim O, Glushkova Olga V, Avkhacheva Nadezhda V, Safronova Valentina G, Fesenko Evgeny E
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russian Federation.
Eur J Pharmacol. 2009 Aug 1;615(1-3):234-40. doi: 10.1016/j.ejphar.2009.05.004. Epub 2009 May 20.
The effects of mixed dietary coenzyme Q(9), alpha-tocopherol, and beta-carotene on immune cell activity and blood cytokine profile were studied in peritoneal macrophages, spleen lymphocytes, and blood plasma from mice with acute inflammation induced by lipopolysaccharide (LPS). The activity of each fat-soluble antioxidant was also investigated separately in several model systems, both in vivo and in vitro. NMRI male mice were fed a diet supplemented with fat-soluble antioxidants for 15 days prior to LPS injection. LPS-induced inflammation resulted in induction of cellular production of pro-inflammatory cytokines such as TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-6, IFN-gamma, and also IL-10, an anti-inflammatory cytokine, and subsequent accumulation of these cytokines in blood plasma. In animals fed the antioxidant-rich diet, the inflammatory response to LPS injection was significantly reduced. The production of anti-inflammatory cytokine IL-10 in response to toxic stress and its accumulation in plasma were not modified by the diet. In addition, the expression of the inducible form of heat-shock protein 70 in mice treated with endotoxin was reduced in the animals pretreated with the antioxidant-rich diet. We showed that the diet suppressed phosphorylation of NF-kappaB, I kappaB kinase and SAPK/JNK proteins, thereby preventing the activation of the NF-kappaB kinase and SAPK/JNK signaling pathways in LPS-treated mice. In this report we demonstrate the potential effectiveness of naturally occurring antioxidant nutrients in the reduction of the inflammatory response. Therefore, it may be possible to develop novel therapeutic combinations, containing coenzyme Q(9), alpha-tocopherol, and beta-carotene, which promote immune stimulation.
研究了混合膳食辅酶Q(9)、α-生育酚和β-胡萝卜素对脂多糖(LPS)诱导的急性炎症小鼠腹膜巨噬细胞、脾淋巴细胞和血浆中免疫细胞活性及血液细胞因子谱的影响。还在体内和体外的多个模型系统中分别研究了每种脂溶性抗氧化剂的活性。在注射LPS前15天,给NMRI雄性小鼠喂食补充了脂溶性抗氧化剂的饮食。LPS诱导的炎症导致促炎细胞因子如TNF-α、IL-1α、IL-1β、IL-2、IL-6、IFN-γ以及抗炎细胞因子IL-10的细胞产生增加,随后这些细胞因子在血浆中积累。在喂食富含抗氧化剂饮食的动物中,对LPS注射的炎症反应显著降低。饮食对毒性应激诱导的抗炎细胞因子IL-10的产生及其在血浆中的积累没有影响。此外,在内毒素处理的小鼠中,用富含抗氧化剂的饮食预处理的动物中热休克蛋白70诱导型的表达降低。我们发现该饮食抑制了NF-κB、IκB激酶和SAPK/JNK蛋白的磷酸化,从而阻止了LPS处理小鼠中NF-κB激酶和SAPK/JNK信号通路的激活。在本报告中,我们证明了天然存在的抗氧化营养素在减轻炎症反应方面的潜在有效性。因此,有可能开发出含有辅酶Q(9)、α-生育酚和β-胡萝卜素的新型治疗组合,以促进免疫刺激。