Effects Of HMGB1 A-box Intervention On Macrophage Polarization And Its Inflammatory Response In Hp Infection

Background and purpose: The average infection rate of Helicobacter pylori(Hp)in our country exceeds 50%,and it is generally difficult for the body to clear spontaneously after infection,which can lead to gastrointestinal diseases such as gastritis and gastric ulcer,but its immune pathogenic mechanism is unknown.Macrophage(Mφ)polarization is an important factor affecting Hp infection-induced gastric mucosal inflammatory response,but its regulatory mechanism remains to be studie d.High mobility group B1(HMGB1)released under infection conditions can bind to receptors on the surface of macrophages and participate in the occurrence and development of inflammatory responses.The previous study of the research group found that Hp infection can induce gastric epithelial cells to release HMGB1,which binds to TLR4 receptors and participates in gastric mucosal inflammation.However,the role of HMGB1 in Hp infectious gastritis is currently studied.Less,its regulation on macrophage polarization has not yet been reported.This article aims to preliminarily investigate the effect of HMGB1 regulation on macrophage polarization in H.pylori infection.Methods: Mouse bone marrow stem cells were obtained,induced to differentiate into bone marrow-derived macrophages(BMM)by M-CSF,and their characteristic surface molecules F4/80 and CD11 c were identified by immunofluorescence;Hp-infected mouse pregastric cancer cells were constructed strain(MFC)and BMM co-culture system,using HMGB1 inhibitor A-box for intervention experiment,collecting cell samples and culture supernatant,and detecting the expression of HMGB1 in BMM cells in Hp infection by Real-time PCR,Western Blot and ELISA respectively and the effect of HMGB1 regulation on Hp-induced macrophage polarization and inflammatory mediator release.Results: Bone marrow stem cells can be successfully induced to differentiate into BMM with a certain concentration of M-CSF;Hp infection can down-regulate the expression of HMGB1 in BMM cells(p<0.05),and promote the release of HMGB1,TNF-α,IFN-γ and other inflammatory mediators(p<0.05),and the expression of i NOS,a representative molecule of M1 cells induced by BMM,was up-regulated(p<0.05),and the HMGB1 inhibitor A-box could inhibit its effect;while the content of IL-4 and the expression of Arg-1 in BMM cells in Hp infection There was no statistical difference(P>0.05),and the content of IL-10 was down-regulated(p<0.05).Conclusion: Hp infection can promote the polarization of m acrophages to M1 type cells,promote the release of inflammatory mediators such as HMGB1,TNF-α,IFN-γ and other inflammatory mediators in macrophages,and aggravate the inflammatory response induced by them.HMGB1 inhibitor A-box can inhibit the its effect.