Abstract:

Objective To explore the potential mechanism of Helicobacter pylori（H. pylori）metabolites in regulating the secretion of inflammatory factors. Methods After infection with E. coli（E.Coli）or H. pylori，the secretion level of key inflammatory factors IL⁃33，TNF⁃α and IFN⁃γ in human gastric cancer cells AGS was detected. Twenty⁃four hours after H.pylori infection of AGS cells，the cell supernatant was collected for liquid chromatogra⁃ phy and tandem mass spectrometry to detect H. pylori metabolites，and key metabolites were identified by screen⁃ ing. Results After E.Coli or H. pylori infection，the secretion level of IL⁃33，TNF⁃α and IFN⁃ γ in AGS cells increased. Compared with E. coli infection，AGS cells infected with H. pylori secreted lower level of IL⁃33，TNF⁃α， and IFN⁃γ. The H. pylori metabolite adenosine decreased the secretion level of IL⁃33，TNF⁃α and IFN⁃γ in a gradi⁃ ent⁃dependent manner. Adenosine level of AGS cells were not significantly changed after infection with adenosine synthase knockout strain H. pyloriΔAdA strain. After H. pyloriΔAdA infection，the secretion level of IL⁃33，TNF⁃α，and IFN⁃ γ in AGS cells was higher than that in H. pyloriWT⁃infected AGS cells. After knockdown of A2A receptor， the secretion level of IL⁃33，TNF⁃ α，and IFN⁃ γ increased in H. pylori⁃infected AGS cells. Four weeks after H. pyloriΔAdA or wild⁃type H. pyloriWT infection of mice，the level of IL⁃33，TNF⁃α，and IFN⁃γ in the serum of mice all increased. The level of IL⁃33，TNF⁃α and IFN⁃ γ in the serum of mice after H. pylori Δ AdA infection increased significantly. In addition ，the titers of anti ⁃H.pylori antibodies produced in mice after H. pylori Δ AdA infection increased. Conclusion Adenosine synthase expressed by H. pylori can promote the production of adenosine，and then adenosine regulates the secretion of inflammatory factors of IL⁃33，TNF⁃α and IFN⁃γ through A2A receptors， and reduces the level of adaptive immunity.

Key words:

Helicobacter pylori, metabolites, inflammatory factors, adenosine, A2A receptors