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

Abstract

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.

Keywords

Helicobacter pylori / T helper cells / gastric cancer / interleukin-17A / RORγt

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