探討樟芝化合物SY-1在食物過敏中對樹突細胞功能之免疫抑制作用

Abstract

食物過敏是指對食物中的蛋白有異常、過度之免疫反應。樹突細胞 (Dendritic cells) 在啟動免疫反應及引起食物過敏中扮演重要角色。樟芝 (Antrodia cinnamomea) 是傳統中藥材，研究指出從樟芝分離出來的4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) 具有抗癌症效果。本研究探討SY-1對於樹突細胞之免疫調節功能及其在食物過敏中潛在的療效。霍亂毒素 (Cholera toxin)是 研究食物過敏中最常用的黏膜佐劑。研究結果指出，SY-1能有效地抑制霍亂毒素誘發活化樹突細胞後，細胞表面MHC II及Costimulatory molecule (CD40, CD80, CD86)表現及多種細胞激素與趨化激素的產生；於試管 (in vitro) 或活體 (in vivo) 實驗中，SY-1可抑制樹突細胞移動能力。藉由口服餵予卵白蛋白 (ovalbumin；OVA) 及霍亂毒素，在BALB/c小鼠中建立食物過敏的動物疾病模式，經致敏化的小鼠產生抗原專一性E型免疫球蛋白 (OVA-specific IgE) 和過敏性反應 (anaphylacxis) ，脾臟細胞也會對OVA反應，引起抗原專一性的細胞增生及分泌細胞激素IL-4, IL-5, IL-13和IFN-γ；相對的，對照組小鼠並無這些反應。在每次致敏化小鼠時口服給予SY-1，利用食物過敏的動物疾病模式，進一步探討SY-1的免疫抑制作用，結果顯示，接受口服SY-1的小鼠，其血清中OVA專一性IgE較低，之後經口攝入OVA時不會產生顯著的過敏症狀，此外，脾臟細胞的OVA專一性細胞增生及細胞激素分泌反應較輕微。由上述結果可知，藉由抑制樹突細胞活化及功能，SY-1對於食物過敏具有潛在的療效。

Food allergy is an immune-mediated adverse reactivity to food proteins. Dendritic cells (DCs) are critical in initiating an immune response and play an important role in establishing food allergy. 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) isolated from Antrodia cinnamomea (AC), a medicinal fungus, is reported to possess antitumor properties. In this study, the immunomodulatory effects of SY-1 on DCs and the therapeutic potential against food allergy were examined. Cholera toxin (CT) is the most commonly used mucosal adjuvant in food allergy. SY-1 effectively inhibited CT-induced DC activation by reducing the expression levels of MHC class II and costimulatory molecules and the production of proinflammatory cytokines/chemokines. In addition, CT-induced DC migration was diminished by SY-1 for both in vitro and in vivo model. The murine model of food allergy has been established in BALB/c mice by oral feeding with OVA plus CT. OVA-specific IgE and anaphylacxis were provoked in sensitized mice. OVA-specific cell proliferation and IL-4, IL-5, IL-13 and IFN-γ cytokine production were induced in spleen. In contrast, these phenomena were absent in the control mice. Oral administrated of SY-1 during each sensitization to investigate the immunosuppressive effect of SY-1 in the murine model of food allergy. Serum OVA-specific IgE were markedly declined in mice fed with SY-1. These mice were protected from anaphylaxis after OVA challenge. Furthermore, SY-1 significantly ameliorated OVA-specific cell proliferation and cytokine production of splenocytes. Taken together, these results suggest that SY-1 may have therapeutic potential against food allergy by suppressing DC activation and function.