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

在我们之前的研究中，我们发现BALB/c小鼠联合给予β-胡萝卜素和高α-生育酚可抑制特异性抗原诱导的IgE抗体的产生。为了弄清这种抑制的机制，我们进行了几项实验。2004年，研究了小鼠体内影响IgE产生的细胞因子的产生。体外抗原提呈实验表明，给予β-胡萝卜素和高α-生育酚的小鼠脾细胞产生抗原诱导型IL-12的能力增强。由于BC被维甲酸酯取代后作用消失，故考虑其氧化还原活性而不是维生素A原活性的参与。2005年，我们发现BC在小鼠巨噬细胞系RAW264中诱导谷胱甘肽的合成，并伴随着γ-谷氨酰半胱氨酸合成酶轻链的诱导，而BC则氧化细胞膜。谷胱甘肽的合成导致细胞质抗氧化，从而影响细胞因子mRNAs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的氧化作用，也不影响细胞质的抗氧化作用，也不影响细胞因子mRNA的产生。基于上述结果，我们在2006年试图阐明BC促进给予一定剂量AT的小鼠分泌IL-12的机制。主要结果是，BC可剂量依赖性地上调脾细胞内GSH浓度。也有关于抗原提呈细胞中谷胱甘肽(S)的含量与IL-12分泌的相关性的报道，结合上述研究，我们得出结论，摄入BC可导致抗原提呈细胞胞浆的抗氧化变化，这有助于促进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.