吸菸與許多的疾病有關，它造成細胞氧化性傷害誘發細胞凋亡，並且影響細胞激素產生。間白素15 (Interleukin 15, IL-15)是一種在人類呼吸道上皮細胞內持續表現mRNA的細胞激素，與IL-2相關。IL-15和IL-2有各自的受器alpha鏈和彼此共用分享的受器beta鏈與gamma鏈。IL-15會刺激B細胞、T細胞和自然殺手之細胞增生、活化及聚集。此外，IL-15利用和Axl 受器酪氨酸磷酸激酶 (Axl receptor tyrosine kinase)之間的transactivation保護纖維母細胞免於細胞凋亡。在本研究中，以香菸萃取物(cigarette smoke extract, CSE) 或是酯多醣體 (lipopolysaccharide, LPS)誘發發炎反應，進而研究IL-15與其相關的IL-2在人類呼吸道上皮細胞中的表現。以反轉錄聚合酶鏈鎖反應(RT-PCR)和即時PCR反應偵測基因表現。細胞表面和分泌至培養液中的蛋白質分別以流式細胞儀和酵素吸附免疫反應進行測量。結果顯示CSE可延長LPS引起的發炎反應並獨立誘發IL-15和IL-2 RNA的表現。IL-15蛋白質無法在培養液中發現，只在細胞膜上可偵測到，此結果表示IL-15訊號可能是使用transpresentation方式傳遞。IL-15蛋白質會受到CSE 刺激而增加，IL-15受器□鏈蛋白質也會隨著CSE濃度增加而提高。同樣地IL-15和Axl RNA表現也會因CSE誘發而增加。提高IL-15、IL-15受器alpha鏈以及Axl的表現，暗指此三者在抵抗CSE所誘發的細胞凋亡中具有協同性作用。本研究顯示CSE在發炎反應中對IL-15 RNA和蛋白質的影響，IL-15表現可能為CSE加劇呼吸道發炎反應的因素之ㄧ。

Cigarette smoke is related to many diseases. It causes cells oxidative damage and apoptosis, and affects the production of many cytokines. Interleukin 15 (IL-15) is a cytokine correlated with IL-2, and expressed mRNA constitutively in human airway epithelial cell. IL-15 receptor uses its own □ chain but shares the □ and □ chain with IL-2 receptor. IL-15 stimulates the proliferation, activation and recruitment of B cells, T cells and natural killer cells. IL-15 also transactivates the Axl receptor tyrosine kinase to protect fibroblast from apoptosis. This study was designed to investigate the responses of IL-15 as well as IL-2 against the inflammatory process induced by cigarette smoke extract (CSE) or lipopolysaccharide (LPS) in human airway epithelial cells. The gene expression were detected by reverse transcription polymerase chain reaction (PCR) and real-time PCR. The protein level in secrete form and cell surface investigated by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. The results showed CSE prolonged the inflammation caused by LPS and induced the IL-15 and IL-2 mRNA expression independently. The presence of IL-15 protein was only detected on the cell membrane but not in the culture medium. This result suggested the signal transduction of IL-15 was through the way of transpresentation. The protein of IL-15R□ was increased when the concentration of CSE raised. And the mRNA of IL-15 and Axl was also induced by CSE. Increased Axl, IL-15 and IL-15R□ expression implied their synergistic role of resisting the CSE induced apoptosis. This study demonstrated the effect of CSE on the expression of IL-15 RNA and protein production during the inflammatory process. The IL-15 expression resisting CSE-induced apoptosis could be one of potential factors that CSE enhances the severity of airway diseases.

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