The Synergy Of Helicobacter Pylori And Lipid Metabolic Disorders In Induction Of Thl7-related Cytokines In Human Gastric Cancer

Helicobacter pylori(H.pylori),a gram-negative spiral-shaped pathogenic bacterium,specifcally colonizes and induces damage to the gastric epithelium leading to chronic gastritis,ulcers and even cancer.Autoimmune reaction was activated when helicobacter pylori colonized in the stomach.By recruiting lymphocytes and Th cells,such as Th1,Th2,Th17 cells,the body could defend itself.Relative immune cells can release inflammatory cytokines such as IL-6,IL-17A,granulocyte-macrophage colony stimulating factor(GM-CSF)to trigger inflammation.And long-term inflammation eventually results in gastric cancer.Many studies have demonstrated that a mixed response of Thl and Th17 cells plays a critical role in H.pylori-induced inflammatory gastric diseases and cancer.H.pylori elicits Thl response to produce interferon-?(IFN-?)and tumor necrosis factor-a(TNF-a)causing chronic gastritis and ulcers.Th17 cells are also frequently recruited by H.pylori to the gastric mucosa,and are characterized by expression of interleukin(IL)-17A/F,GM-CSF,IL-21,IL-22 and IL-23,and the transcription factor of ROR?t.Th17 cells can be further activated in tumor microenvironment due to these cytokines.It has been reported that obesity can worsen the process of Helicobactor-associated gastric cancer.However,the cross-talk between H.pylori infection and metabolic disorders in the gastric carcinogenesis remains not completely understood.42 gastric cancer cases were provided by the Tumor Hospital,and the clinical datas were collected.After getting their cDNA,qRT-PCRwas performed.By testing the expression of IL-6,Leptin,GM-CSF,CXCL1,we discussed the effects of helicobacter pylori infection to Th17 differentiation and response.In addition,we collected a number of specimens of gastric ulcer,and used these specimens to explore the relationship between H.pylori infection and gastric inflammation.As a result,we found that helicobacter pylori-associated increase of IL-17A was enhanced in the group with higher plasma triglycerides,and H.pylori infection and lipid metabolic disorders could synergistically increase IL-17A expression.On the other hand,helicobacter pylori infection could promote the expression of IL-6 and lepti which could regulate Th17 differentiation.At the same time,the expression of GM-CSF and CXCL1 was upregulated,and their expression was correlated with the expression of IL-17A.Interestingly,RORyt,a transcription factor regulating Th17 differentiation,was increased 6-fold in H.pylori-positive vs.negative tumors.Further elevation of RORyt was seen in advanced H.pylori-associated tumors.Moreover,we observed that H.pylori-associated increase of IL-17A was enhanced in the group with higher plasma triglycerides.In summary,we demonstrate that H.pylori infection and abnormal lipid metabolism can exert a synergistic role in Thl7 activation and response to promote GC development.