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  • 學位論文

胃幽門螺旋桿菌感染病人血清中之抗體可增強病原熱休克蛋白60誘發前發炎性細胞激素產生的活性

Antibodies in the sera of patients with Helicobacter pylori infection promote the activities of pathogenic heat shock protein 60 to induce the expressions of proinflammatory cytokines

指導教授 : 廖光文

摘要


胃幽門螺旋桿菌的熱休克蛋白 (HSP60s) 誘導前發炎性細胞激素(proinflammaroty cytokine) 的表現跟胃部發炎有很大的關連性。在臨床的研究中,胃幽門螺旋桿菌感染病人的血清裡可以偵測到抗胃幽門螺旋桿菌熱休克蛋白60抗體。令人感到驚訝的,16位患有胃癌、胃炎、十二指腸潰瘍或胃潰瘍病人的血清並無法中和重組胃幽門螺旋桿菌熱休克蛋白60 誘導腫瘤壞死因子-甲型 (TNF-alpha) 和介白素-8 (IL-8) 的釋放,反而增加前發炎性細胞激素的表現。研究結果顯示,不論來自何種物種的抗胃幽門螺旋桿菌熱休克蛋白60多株抗體 (anti-HpHSP60 polysera) 都可以影響胃幽門螺旋桿菌熱休克蛋白60增加腫瘤壞死因子-甲型和介白素-8的表現。更近一步研究發現此增強效應為血清中專一抗胃幽門螺旋桿菌熱休克蛋白60抗體所導致,而非血清中其他因子或非專一性抗體。最後,實驗結果推測Fc接受器 (Fc receptor) 在抗胃幽門螺旋桿菌熱休克蛋白60抗體增加發炎的影響中扮演一個角色。綜合這些研究結果,我們揭露當胃幽門螺旋桿菌熱休克蛋白60存在時,病人血清中的抗胃幽門螺旋桿菌熱休克蛋白60抗體可能造成更嚴重的發炎。這樣的發現可能可以提供未來胃幽門螺旋桿菌感染病人在臨床上治療的應用。

並列摘要


H. pylori-derived heat shock proteins (HSP60s) are closely associated with gastric inflammation to induce the expressions of proinflammatory cytokines. In clinical examination, anti-HpHSP60 antibodies could be detected in H.pylori-postive patients’ sera. Surprisingly, the sera from 16 patients with gastric cancer, gastritis, duodenal ulcer or peptic ulcer could not neutralize the activities of recombinant HpHSP60 to induce releases of TNF-alpha and IL-8 but they raised the expressions of proinflammatory cytokines. The results showed the no matter what species’ anti-HpHSP60 polysera all could cause an enhancive effect on HpHSP60 to induce TNF-alpha or IL-8 expression. Furthermore, the specific antibodies in sera but not other factors or non-specific antibodies contributed to the enhancive effect. Finally, the results suggested Fc receptor plays a role in the enhancive effect of anti-HpHSP60. Together these results, we explored that the patients’ anti-HpHSP60 antibodies in sera may result in more serious inflammation in the presence of HpHSP60. This finding may provide further application in clinical treatments for the patients with H. pylori infection.

參考文獻


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