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.