Lipoxin A4 attenuates Helicobacter pylori-induced gastric mucosal inflammation through promoting inflammatory resolution.

PURPOSE: This study focus on the protective effects of lipoxin A4 (LXA4) against Helicobacter pylori (H. pylori) infection in mice. METHODS: Twenty four specific pathogen-free (SPF) C57BL/6 J mice were assigned to four groups: control, H. pylori, H. pylori + lipoxin A4 (LXA4), and H. pylori + LXA4 + BOC-2 groups. Mice in the infected groups received daily oral gavage of 0.5 mL H. pylori suspension (1 × 10⁸ CFU/mL) for three consecutive days. Mice were intraperitoneally injected with LXA4 at 0.5 μg per 0.1 mL every two days over two weeks. BOC-2, a selective antagonist of formyl peptide receptor 2 (FPR2, the specific receptor of LXA4), was administered via a single intraperitoneal injection at 30 μg/kg 72 h before euthanasia. Gastric antrum mucosal pathological lesions were evaluated by hematoxylin-eosin (HE) staining. Flow cytometry was adopted to quantify the infiltration of neutrophils and macrophages, and immunofluorescence co-localization staining was performed to detect Gr-1 and caspase-3.The levels of multiple inflammatory biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA), and western blotting was used to detect target protein expression in gastric corpus tissues. RESULT: Relative to control mice, H. pylori infection induced prominent gastric mucosal injury, alongside increased tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), and LXA4 levels. LXA4 supplementation alleviated H. pylori-triggered gastric pathological lesions and inflammatory responses, while boosting macrophage phagocytosis and neutrophil apoptosis. These protective effects of LXA4 were partially abrogated by BOC-2. CONCLUSION: LXA4 confers prominent protection against H. pylori-triggered gastritis, largely by restraining excessive inflammatory cytokine secretion and modulating neutrophil recruitment during H. pylori infection.