探討霍山石斛之免疫多功能性及誘導單核細胞球產生IL-1ra之機轉

Abstract

摘要 霍山石斛是一個珍貴且富有多功能性的中草藥，具有預防癌症以及抗發炎的傳聞。然而，此中草藥之免疫活性探討目前僅限於在體外研究中少量細胞激素(Cytokine)及趨化素(Chemokine)的研究。在我們的研究中，第一，探討了從霍山石斛萃取的多醣體對老鼠的活體實驗或是人類免疫細胞中，所誘發一系列的細胞激素或趨化素的表現。我們發現石斛多醣在老鼠活體以及人類免疫細胞中，可以誘導包括第一型輔助型T細胞之細胞激素，第二型輔助型T細胞之細胞激素，發炎性細胞激素以及趨化素。第二，我們證明了在老鼠活體中實驗中石斛多醣可以刺激脾臟細胞的增生，也刺激增生了包括CD4 T細胞、CD8 T細胞、B細胞、自然殺手細胞、自然殺手T細胞、單核細胞、巨噬細胞、顆粒型細胞以及調控型T細胞等多種免疫細胞。在我們的研究中還發現了值得注意的一點，也就是石斛多醣可以在老鼠活體以及人類免疫細胞中，特別是單核細胞，誘導一種抗發炎物質稱為細胞激素1(IL-1)接受器的拮抗蛋白(IL-1 receptor antagonist, IL-1ra)。石斛多醣在老鼠血清中誘發的IL-1ra含量超過了細胞激素1β(IL-1β)多達10倍以上，這現象顯示了IL-1ra所引導之抗發炎反應會勝過IL-1β引導的發炎反應。在石斛多醣所誘導IL-1ra之訊息傳遞鏈上，我們證明了ERK/ELK，p38MAPK，PI3K以及NFκB有扮演重要的角色。最後，我們比較並發現了石斛多醣所誘發之IL-1ra的量顯著的超越了F3(F3是一種從另一相當受歡迎之中草藥靈芝所萃取出來之多醣體)所誘發的量。這些結果顯示了石斛多醣對於舒緩IL-1所造成的免疫疾病上，有著巨大的應用價值。

Abstract Dendrobium huoshanense is a valuable and versatile Chinese herbal medicine with the anecdotal claims of cancer prevention and anti-inflammation. However, its immunological activities are limited to in vitro studies on a few cytokines and immune cell functions. First, we investigated the effects of polysaccharides isolated from DH (DH-PS) on inducing a panel of cytokines/chemokines in mice in vivo and human in vitro. We found that DH polysaccharides (DH-PS) induced TH1, TH2, inflammatory cytokines and chemokines in mouse in vivo and human cells in vitro. Secondly, we demonstrated that DH-PS expanded mouse splenocytes in vivo including CD4+ T cells, CD8+ T cells, B cells, NK cells, NKT cells, monocytes/macrophages, granulocytes and regulatory T cells. Notably, DH-PS induced an anti-inflammatory molecule, IL-1ra, in mouse and human immune cells, especially monocytes. The serum level of IL-1ra elicited by the injection of DH-PS was over 10 folds of IL-1β, suggesting that DH-PS-induced anti-inflammatory activities might over-ride the inflammatory ones mediated by IL-1β. The signaling pathways of DH-PS-induced IL-1ra production was shown to involve ERK/ELK, p38 MAPK, PI3K and NFκB. Finally, we observed that IL-1ra level induced by DH-PS was significantly higher than that by F3, a polysaccharide extract isolated from another popular Chinese herbal medicine, Ganoderma lucidum. These results indicated that DH-PS might have potential applications for ameliorating IL-1-induced pathogenic conditions.