標題: | 研究幽門螺旋桿菌熱緊迫蛋白60的功能---誘發宿主Treg細胞增加藉以抑制T細胞之活性 Study of H. pylori Heat Shock Protein 60 on the Suppression of T-Cell Proliferation by Induction of Treg Cell |
作者: | 廖光文 Liao Kuang-Wen 國立交通大學生物科技學系(所) |
關鍵字: | 幽門螺旋桿菌熱休克蛋白60;調控型T細胞 |
公開日期: | 2010 |
摘要: | 幽門螺旋桿菌於1980年代末期被發現以來,即成為胃腸科疾病及胃癌成因的重要 研究課題。此菌已被證實可造成人類胃上皮細胞的破壞、癌變以及抑制宿主免疫系統等 現象。在本實驗室的研究中發現,幽門螺旋桿菌的熱迫性蛋白60(HpHsp 60)可使巨噬 細胞產生較高量之IL-10及TGF-β以及多種發炎性細胞激素,此外HpHsp 60亦會促使腫 瘤細胞遷移能力及血管新生成能力增加,故HpHsp 60對宿主而言應屬一種致病因子,再 者HpHsp 60可結合至TGF-β受體II啟動TGF-β的SMAD訊息傳遞路徑。根據文獻指出 TGF-β對調控性T細胞(Treg cells)功能十分重要,因此可預見HpHsp 60對調控性T 細胞應有重要影響。而調控性T細胞已被認定對免疫反應的抑制扮演重要的角色,因此 HpHsp 60應對宿主免疫抑制作用的形成占有重要地位。故於本計劃將研究HpHsp 60對調 控性T細胞的影響,本研究室預計探討幽門螺旋桿菌之Hsp60可能以調控性T細胞造成免 疫抑制現象及機制。是以本計畫之主要目的為: (1) 研究HpHsp60是否對調控性T細胞 功能上有何影響。(2) 探討幽門螺旋桿菌Hsp60分子的作用位置及其作用機制對調控性T 細胞增生的影響。(3) 探討HpHsp60刺激後的巨噬細胞及其所產生的細胞激素是否會對 調控性T細胞的生成或功能有影響。希望藉此研究能提供有用的資訊於未來有利於發展 藥物或疫苗以治療幽門螺旋桿菌引起的相關疾病。 Helicobacter pylori (H. pylori, Hp) has become an important issue in the field of gastrointestinal disease and the development of gastric cancer since its discovery in late 1980’s. It has been confirmed that Hp can damage human gastric epithelial cells, cause oncogenesis and suppress host’s immunity. Our results indicated that H. pyori heat shock protein 60 (HpHsp60) could induce macrophage to increase the high expression of IL-10, TGF-β, and other proinflammatory cytokines. In addition, HpHsp60 also enhanced the abilities for migration of tumor cell and angiogenesis. Thus, it should be a pathogenic factor for host. Moreover, HpHsp60 could bind to TGF-β receptor II and trigger TGF-β regulated SMAD signal pathway. According to the published literatures, TGF-β is an important factor for the function of regulatory T cells (Treg cells). Therefore, HpHsp60 should have certain important effect on the function of Treg cells. Besides, Treg cells have been considered as an important role for immunosuppression. So, HpHsp60 should be important for the host immunity to tolerate the infectious microbial. In this plan, we are going to investigate whether the HpHsp60 can cause immunosuppression through induction of Treg cells. The goads in this plan are: (1) to investigate whether the HpHsp60 can affect the induction or function of Treg cell, (2) to study the effective sequence of the HpHsp60 for the induction or function of Treg cell, (3) to investigate whether the HpHsp60-stimulated macrophage or its secretary cytokines can affect the induction or function of Treg cell. We hope these results can provide useful information to develop drug or vaccine for the therapy of H. pylori-induced diseases. |
官方說明文件#: | NSC99-2320-B009-002 |
URI: | http://hdl.handle.net/11536/100265 https://www.grb.gov.tw/search/planDetail?id=2148337&docId=345832 |
顯示於類別: | 研究計畫 |