幽門螺旋桿菌熱休克蛋白60N端之活性

Abstract

幽門螺旋桿菌的感染與許多上消化道的疾病相關，像是慢性胃 炎、消化性潰瘍、黏膜相關淋巴組織淋巴癌 （MALT lymphoma）以 及胃癌。感染幽門螺旋桿菌患者若無以抗生素加以治療，將轉變為慢 性、持續性感染 ; 而上述疾病的發生則主要起因於該病原菌的慢性 感染。並且該菌所分泌的熱休克蛋白60 已被證實為一黏附分子可連 結幽門螺旋桿菌以及人類胃上皮細胞，進而造成胃部疾病。 對於幽門螺旋桿菌熱休克蛋白60 在免疫調節功能上，較多的研 究是指出此蛋白可引發前發炎激素（pro-inflammatory cytokine）例 如：干擾素-g （IFN-g）、腫瘤壞死因子-a（TNF-a）、白介素6、8 （IL-6、8）而引起發炎反應。特別是在氨基酸序列300 到435 的位 置可引發大量IL-8 的表現。在另一方面，近年來也有研究指出不同 物種的熱休克蛋白60 似乎在人體免疫系統可以抵禦病原菌的慢性感 染。例如人類與日本血吸蟲的熱休克蛋白60 可引發調節型T 細胞 （regulatory T cells）的增生達到免疫抑制的效果。然而，幽門螺旋桿 菌熱休克蛋白60 對於免疫調節的機制依然不清楚。在本篇實驗中， 我們利用人類周邊血液單核球細胞（ human peripheral blood mononuclear cells, PBMCs）作為研究系統，探討幽門螺旋桿菌熱休 克蛋白60 之N 端蛋白對其增生所造成之影響。研究結果顯示，幽門 螺旋桿菌熱休克蛋白60 之N 端位置於101-200 和1-200 之蛋白能夠 降低PBMCs 之增生以及引發TGF-b之產生。根據上述研究結果，幽 門螺旋桿菌熱休克蛋白60 可藉由接近N 端的101-200 之處引發 TGF-b並且達到免疫抑制的效果。

Helicobacter pylori can lead to variety of upper gastrointestinal disorders, such as chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Without treatment, H. pylori would become chronic infection in almost all of those patients. The expression of heat shock protein 60 by H. pylori (HpHSP60) has been shown as an adhesion molecule that interacts with host gastric epithelial cells. For immunoregulation, many literatures showed that HpHSP60 can induce the secretions of pro-inflammatory cytokines, such as IFN□g, TNF-a, IL-□6, IL-8 and cause inflammation. Particularly, the sequence of HpHSP60 from 300 to 435 can induce dramatically IL-8 expression. Interestedly, researchers found that HSP60 in different species seems to be related to the regulation of immune responses in chronic infection disease. Literatures indicated that HSP60 in human and S. japonicum can induce regulatory T cell (Treg) expression and suppress immunity. However, the feature of HpHSP60 for immunoregulation still remains unknown. In this study, the N-terminal domains of HpHSP60 were constructed and measured their activities on immune response. The results showed that the treatment with the sequence 101-200 (HpHSP60101-200) or 1-200 (HpHSP601-200) of HpHSP60 to human peripheral blood mononuclear cells (PBMCs) decreased the proliferation rate. Furthermore, HpHSP60101-200 and HpHSP601-200 could increase TGF-b secretion from THP-1 cells. Taken together, the sequence of HpHSP60 from 101 to 200 could induce the expression of TGF-b and which may have contributions to their immune suppressive activity.