Quercetin ameliorates Helicobacter pylori‐induced gastric epithelial cell injury by regulating specificity protein 1/lipocalin 2 axis in gastritis

Abstract Helicobacter pylori (HP) infection is the main cause of most cases of gastritis. Quercetin has been shown to have anti‐inflammatory, anti‐bacterial, and antiviral activities and has been demonstrated to be involved in HP‐induced gastric mucosa injury. Moreover, the secretory protein lipocalin‐2 (LCN2) was elevated in HP‐infected gastric mucosa. Thus, this work aimed to study the interaction between quercetin and LCN2 in HP‐triggered gastric injury during gastritis. Human gastric epithelial cell line GES‐1 cells were exposed to HP for functional experiments. Cell viability, apoptosis, and inflammation were evaluated by cell counting kit‐8, flow cytometry, and enzyme‐linked immunosorbent assay, respectively. Levels of genes and proteins were tested using quantitative reverse transcription polymerase chain reaction and western blotting analyses. The interaction between LCN2 and specificity protein 1 (SP1) was validated using chromatin immunoprecipitation assay and dual‐luciferase reporter assay. Thereafter, we found quercetin treatment suppressed HP‐induced GES‐1 cell apoptotic and inflammatory injury and macrophage M1 polarization. LCN2 was highly expressed in HP‐infected gastritis patients and HP‐infected GES‐1 cells, while quercetin reduced LCN2 expression in HP‐infected GES‐1 cells; moreover, LCN2 knockdown reversed HP‐induced GES‐1 cell injury and macrophage M1 polarization, and forced expression of LCN2 abolished the protective effects of quercetin on GES‐1 cells under HP infection. Mechanistically, SP1 bound to LCN2 promoter and promoted its transcription. Also, SP1 overexpression counteracted the functions of quercetin on HP‐stimulated GES‐1 cells. In all, quercetin ameliorated HP‐induced gastric epithelial cell apoptotic and inflammatory injuries, and macrophage M1 polarization via the SP1/LCN2 axis.