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

This study focus on the protective effects of lipoxin A4 (LXA4) against Helicobacter pylori (H. pylori) infection in mice.

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.

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.

LXA4 confers prominent protection against H. pylori-triggered gastritis, largely by restraining excessive inflammatory cytokine secretion and modulating neutrophil recruitment during H. pylori infection.