The synergy of Helicobacter pylori and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer  

作　　者：Jie Liu Han Wang Gang Chen Mo Yang Zhi-Xian Wu Russell Erick Ericksen Alice Sze Tsai Wong Weiping Han Jin-Zhang Zeng 

机构地区：[1]Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology,School of Pharmaceutical Sciences,Xiamen University,Xiamen 361102,Fujian,China [2]Department of Pathology,Fujian Provincial Cancer Hospital,Fujian Medical University,Fuzhou 350014,Fujian,China [3]Department of Hepatobiliary Disease,Fuzhou General Hospital(Dongfang Hospital),Xiamen University,Fuzhou 350025,Fujian,China [4]Laboratory of Metabolic Medicine,Singapore Bioimaging Consortium,Agency for Science,Technology and Research,Singapore 138667,Singapore [5]School of Biological Sciences,University of Hong Kong,Hong Kong 999077,China.

出　　处：《Journal of Cancer Metastasis and Treatment》2017年第1期169-176,共8页癌症转移与治疗（英文版）

基　　金：supported by grants from the 10th Singapore-China Joint Research Program(S2014GR0448);Natural Science Foundation of China(NSFC)(81673467,31471273,21303145,31340029,30971445,31501145);Research Grants Council(RGC)of Hong Kong Joint Research Scheme(NSFC/RGC)(31461163002/N_HKU740/14 and 30931160431/N_HKU 735/09);Marine Drug Research Project of South Marine Center(14GYY023NF23);Fujian Province’s 100-Talent Program of Innovation of Science and Technology(201510117);the Fundamental Research Funds for the Central Universities(No.2013121037).

摘　　要：Aim:To study the impact of Helicobacter pylori(H.pylori)and lipid metabolic disorder on the expression of Th17-related cytokines in gastric cancer(GC).Methods:GC specimens were randomly collected from 42 patients,of whom 15 had H.pylori infection and 27 were without.Tumor RNA was extracted for reverse transcription quantitative polymerase chain reaction quantification of gene expression.Results:The mRNA levels of interleukin(IL)-6 and leptin,which are known to regulate Th17 differentiation,were upregulated by 20 and 6 folds,respectively,in H.pylori-infected compared to uninfected patients.IL-17A and granulocyte-macrophage colony-stimulating factor,two cytokines produced by Th17 cells,were 5-and 6-fold higher in tumors with H.pylori infection,respectively.Consistently,RORγt,a transcription factor regulating Th17 differentiation,was increased 6-fold in H.pylori-positive vs.negative tumors.Further elevation of RORγt was seen in advanced H.pylori-associated tumors.In addition,H.pylori infection was also associated with enhanced expression of CXCL1(5 folds),chemotactic factor capable of driving bone marrow-derived immature myeloid cells.Interestingly,we observed that H.pylori-associated increase of IL-17A was enhanced in the group with higher plasma triglycerides.Conclusion:The findings demonstrate a cross-talk and synergistic role of H.pylori infection and abnormal lipid metabolism in GC development,at least partly via cooperative induction of Th17 differentiation and activation.

关 键 词：Helicobacter pylori T helper cells gastric cancer INTERLEUKIN-17A RORΓT 

分 类 号：R57[医药卫生—消化系统]