YT和NK-92細胞株之轉錄因子與細胞激素的後轉錄調控

Abstract

在先天免疫系統中，自然殺手細胞扮演一重要的角色，可直接殺死許多癌細胞和被病毒感染的細胞。例如，受到感染的細胞釋放出干擾素活化自然殺手細胞，進而引起一連串的免疫反應殺死受感染的細胞，簡單來說，它們是用來專門摧毀外來的變質細胞。在眾多干擾素中，γ干擾素較為著名，是受到轉錄因子T-bet所調控。T-bet是屬於T-box家族的轉錄因子，能夠於Th1細胞中表達，作為Th1特異的轉錄因子，誘導出γ干擾素的產生，在Th1細胞與自然殺手細胞發育中起著決定性的作用，為了研究自然殺細胞發育的過程，利用microaray 所分析出來的資料去觀察兩種細胞株(NK-92和YT)中的基因表現，我們發現NK-92是類似於CD56bright 自然殺手細胞而YT則是類似於CD56dim自然殺手細胞。同時，也利用real-time PCR的方式去佐證microaray的結果。最後，我們構築突變的T-bet 基因，送入YT細胞株表現，以western blot的呈現，研究T-bet基因的不同的表現量。

Nature killer cells can mediate cellular cytotoxicity against pathogen infected or malignant cells through releasing a wide variety of cytokines, including IFNg, which is controlled by the transcription factor Tbx21/Tbet. T-bet may also regulate the development of Th1 and nature killer cells. To investigate the developmental process of nature killer cells, we analyzed gene expression profiles of two cell lines derived from NK-cell lymphoma, NK-92 and YT, by microarrays. The expression profile suggests that NK-92 was close to CD56bright NK cell and YT is close to CD56dim NK cell. Interestingly, T-bet was weak in the YT cell line despite strong mRNA expression. Real-time PCR and western blot were performed for confirmation and for dissecting the regulation of T-bet expression.