Hydrogen Promotes the M1 Macrophage Conversion During the Polarization of Macrophages in Necrotizing Enterocolitis.

Abstract

Using a necrotizing enterocolitis (NEC) mouse model alongside RAW264.7 cells and bone marrow-derived macrophages, this study examined how hydrogen influences macrophage polarization. M1 and M2 macrophages were successfully induced, and cytokine profiles, CD16/32, and CD206 expression were assessed by quantitative PCR and flow cytometry. Hydrogen exposure reduced pro-inflammatory cytokines and CD16/32 expression in M1 macrophages, with suppression of CD16/32 also observed in lamina propria-derived macrophages but not in other tissues. Western blot analysis revealed that nuclear NF-κB p65 levels were diminished in both M1 macrophages and the distal ileum of NEC mice. Histological evaluation confirmed a reduction in NEC severity following hydrogen administration. These findings indicate that hydrogen modulates M1 macrophage polarization via NF-κB p65 nuclear suppression, thereby attenuating intestinal inflammation in NEC.

Mechanism

Hydrogen suppresses nuclear translocation of NF-κB p65 in M1 macrophages, leading to reduced pro-inflammatory cytokine production and decreased CD16/32 expression, thereby diminishing intestinal inflammation in necrotizing enterocolitis.