小白鼠細胞素IL－10的訊息傳遞及對轉錄因數AGP/EBP的調控

Abstract

近年來在細胞素（ cytokine ）之訊息傳遞（ signal transduction ）方面的研究有相當的進展， STAT ( signal transduction and activation of transcription ）家族被發現參與許多細胞素的訊息傳遞路徑， STAT 家族具有訊息傳遞以及轉錄活化之雙重功能，其中 ISGF－3α p91 （又名 STAT1α ）參與幹擾素 α/β、 γ（IFNα/β、γ）之訊息傳遞路徑，並可調控早期基因（ early gene ）的表現，為了瞭解 p91 與轉錄因數 AGP/EBP 之間的關係，我製作了抗 P91 之單株抗體，利用抗體為工具，進一步研究 p91 與 AGP/EBP 之間的關係。 此外， mIL-10 為一新的細胞素，關於其訊息傳遞及標的法因的瞭解都不多，雖已知在單核細胞內與 p91 之活化有關，但本論文發現在小白鼠 C127 乳線瘤細胞中仍是由 p91 家族參與傳訊過程。 最後，本論文又試著探討 mIL對 AGP/EBP 基因之調控，發現mIL-10在 C127 細胞中可以促進 AGP 甩 BP 在 RNA 上之表現，所以mIL-10、 P91 與 AGP/EBP 三者之間可能存在著某些微妙的關係。

In recent years, considerable progress has been made on signal transduction pathways of different cytokines. The STAT family of proteins, carrying out dual functions: signal transduction and activation of transcription, are involved in many cytokine-induced signal transductions. p91 (ISGF-3α, STAT1α) was originally identified to be involved in IFN α/β, γ signalling pathway. It has been shown that the activated p91 can stimulate the expression of a set of early genes. In this thesis, anti-p91 monoclonal antibodies were prepared and subsequently used for investigation of IL-10 signal transduction. The signalling pathway of mIL-10 was studied. mIL-10 can activate p91 in monocytes. It can also induce the translocation of p91 family proteins from cytosol to nucleus in C127 cell. mIL-10 can induce the expression of AGPIEBP gene. However, the role of p91 in the mIL-10-induced expression of AGP/EBP remains to be clarified.