辣椒素誘導人類急性白血病單核細胞株分化為第二型吞噬細胞

Capsaicin promotes human acute monocytic leukemia cell’s differentiation into M2 macrophages

黃奕庭(I-Ting Huang)

指導教授 ： 張基隆

高雄醫學大學/醫學院/生物化學研究所/碩士(2014年)

摘要

辣椒素 ( 反8-甲基-N-香草基-6-壬烯酰胺 ) ( Capsaicin, CAP )存在於辣椒果實中，約佔辣椒成分約90%，常被添加於食品中以增加香氣及刺激性。有研究指出辣椒素短期接觸於皮膚時，具致敏性；長期使用後，可促使神經元喪失痛覺功能，達到止痛及消炎的作用。過敏為一種個體受到過敏原( 無毒抗原 )刺激所引發的免疫異常活化反應，此反應與第二型輔助型T淋巴細胞活化相關( T helper 2, Th2 )，長期且經相同過敏原刺激下甚至會進一步活化巨噬細胞( Macrophage )，引發第四型遲發型過敏反應發生。目前研究顯示巨噬細胞又可分為兩種亞型，第一為典型活化巨噬細胞( Classically activated macrophage (M1) )，扮演病原菌吞噬及清除角色；第二為替代型活化巨噬細胞( Alternatively activated macrophage (M2) )，扮演類於第二型輔助型T淋巴細胞角色。
辣椒素是否扮演影響單核細胞 ( Monocyte )分化為M1或M2巨噬細胞效能，並與誘發過敏產生相關，目前仍未釐清，因此本研究透過體外細胞實驗 ( In vitro ) 及動物實驗 ( In vivo )來分析。細胞實驗結果顯示，30 ?嵱的辣椒素可有效促進THP-1細胞株的吞噬 ( Phagocytosis )活性、巨胞飲作用 ( Macropinocytosis )及溶小體 ( Lysosome )表現。在透過分析巨噬細胞亞型基因的表現中可觀察到辣椒素可些微誘導M1巨噬細胞表面標記CD86，以及相關細胞激素IFN-?蚸M酵素iNOS表現上升，但更顯著誘導M2巨噬細胞表面標記CD163及相關細胞激素IL-4、IL-10及酵素精胺酸酶 ( Arginase )、基質金屬蛋白酶2 ( Matrix metalloproteinases2, MMP2 )及基質金屬蛋白酶9 ( Matrix metalloproteinases9, MMP9 )表現增加，顯示辣椒素所誘導的單核細胞分化較傾向於M2巨噬細胞亞型。在動物實驗方面，辣椒素單獨或併用噁唑酮 ( Oxazolone, OXA )誘導過敏模式中亦觀察到，單獨辣椒素刺激下會誘發耳朵腫脹，長時間與噁唑酮共同刺激下將加重過敏發生。此實驗證實，在過敏現象產生時，辣椒素可藉由誘導單核細胞分化成M2巨噬細胞，進而加重過敏反應的發生。

關鍵字

辣椒素

並列摘要

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) accounts for approximately 90% components of chili pepper fruit. It is often added to foods to enhance flavor and spicy. Previous studies indicate that short-term exposure to capsaicin will cause skin allergies; long-term repeated exposure can analgesic and anti-inflammatory by loss of nociceptive neurons. Allergy is an abnormal immune activation of the reaction by the allergen (non-toxic antigen). Among of all of the hypersensitivity reactions, Type IV delayed hypersensitivity reactions is often associated with the activation of the second type helper T lymphocytes (T helper 2, Th2), it could activate macrophage via long-term stimulus by the same allergen. Recent studies have shown that macrophages can be divided into two subsets, one is the classically activated macrophages (M1), has the role of phagocytosis of pathogens; and the other is the alternatively activated macrophages (M2) play the role is similar to the second type helper T lymphocytes.
Whether capsaicin affect monocyte to differentiate into M1 or M2 macrophages and induced allergies, has not yet been clarified. Therefore, this study was to investigate capsaicin’s effect in vitro and in vivo. These results indicated 30 ?嵱 capsaicin could be promote phagocytosis, macropinocytosis and lysosome expression in THP-1 cell line. Analysis of the macrophage subtype gene expression could be observed that capsaicin slightly induced CD86 of M1 macrophage surface marker, and IFN-γ and iNOS expression, but more significantly induced CD163 of M2 macrophage surface marker, and IL-4, IL-10, Arginase, MMP2 and MMP9 expression. Evidence of capsaicin-induced monocytic differentiation more inclined M2 macrophages. In animal experiments, capsaicin alone or in combination with OXA (Oxazolone) induced allergic mode also observed that, capsaicin could induce ear swelling, and aggravation allergy by OXA co-stimulation. This study indicated capsaicin can induce monocyte differentiation into M2 macrophage, thereby increasing the incidence of allergic reactions.

並列關鍵字

Capsaicin

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