A basic research for applying the functional food components to reduce the risk of allergic diseases

在我们以前的研究中，我们发现β-胡萝卜素和高α-生育酚联合喂养BALB/c小鼠抑制特异性抗原诱导的IgE抗体的产生。为了明确这种抑制的机制，我们进行了几个实验。2004年研究了影响IgE产生的小鼠细胞因子的产生。离体抗原呈递实验显示，在来自用β-胡萝卜素和高α-生育酚喂养的小鼠的脾细胞中，抗原诱导型IL-12的产生增加。当BC被视黄酯取代时，由于该作用丧失，因此认为其氧化还原活性的参与代替了维生素原-A活性。我们发现，BC诱导谷胱甘肽的合成伴随着γ-谷氨酰半胱氨酸合成酶的轻链的诱导RAW 264，小鼠巨噬细胞培养细胞系，而BC氧化细胞膜在2005年。谷胱甘肽的合成导致细胞质的抗氧化作用，从而影响细胞因子mRNA的表达。AT虽能抑制自由基引起的细胞膜氧化，但不能抑制BC引起的细胞膜氧化，也不影响细胞质的抗氧化能力和细胞因子mRNA的产生。基于以上结果，我们于2006年试图阐明BC促进小鼠IL-12分泌的机制。作为主要结果，我们发现，细胞内GSH浓度上调，在脾细胞剂量依赖性的BC。还有关于抗原呈递细胞中GSH的量与IL-12分泌相关的报道，结合上述研究，我们得出结论，摄入BC导致抗原呈递细胞的细胞质中的抗氧化变化，这有助于增强IL-12的产生，抑制IgE抗体的产生。

In our previous study we found that combinational feeding of beta-carotene and high alpha-tocopherol to BALB/c mice suppressed the production of IgE antibody induced by the specific antigen. To clear the mechanism underlying this suppression, we have carried out several experiments. The production of cytokine in mice that influence the IgE production was investigated in 2004. An experiment of ex vivo antigen-presentation revealed that the production of the antigen inducible IL-12 was augmented in splenocytes from mice fed with beta-carotene and high alpha-tocohperol. Since the effect was lost when BC was replaced with retinylester, the participation' of its redox activity is instead of provitamin-A activity was considered. We found that BC induced the synthesis of glutathione accompanied by the induction of the light chain of gamma-glutamylcysteine synthetase in RAW264, a murine macrophage cultured cell line, while BC oxidizes the cellular membrane in 2005. The synthesis of glutathione led to the cytoplasmic anti-oxidation which influenced the expression of cytokine mRNAs. Although AT inhibited the oxidization of cellular membrane induced by free-radicals, it could not inhibit the oxidization by BC and it affected neither the anti-oxidization of cytoplasm, nor cytokine mRNA production. Based on above results, we intended to clear the mechanism that BC enhances the IL-12 secretion in mice fed with a fixed amount of AT in 2006. As a main result, we found out that intracellular GSH concentration was up-regulated in the splenocytes dose-dependently on BC. There was also a report of correlating the amount of GSH(s) in an antigen presentation cell and IL-12 secretion, together with the above-mentioned research, we conclude that ingestion of BC results in anti-oxidative change in the cytoplasm of the antigen-presenting-cells, which contributes to enhancing IL-12 production suppressing the production of IgE antibody.