Myeloperoxidase regulates hypoxia-induced inflammation and oxidative stress in liver-spleen axis.

Abstract

BACKGROUND: High-altitude hypobaric hypoxia induces inflammation and oxidative stress, yet the role of myeloperoxidase (MPO) in this pathology remains incompletely understood. This study aimed to investigate whether MPO mediates injury to the liverspleen axis under hypoxic conditions. RESULTS: Using a 3day murine hypoxia model, we unexpectedly found that MPO deficiency exacerbated, rather than mitigated, damage to the liverspleen axis. Compared with hypoxic wildtype mice, MPO-/- mice displayed aggravated histopathological injury, accompanied by excessive phagocyte recruitment and elevated expression of key chemokines (KC, MCP1, MIP2) and proinflammatory mediators (TNFα, IL1β, IL17A). At the molecular level, MPO absence increased splenic protein expression of NFκB, NLRP3, and iNOS, while dysregulating the antioxidant response via the NRF2/HO1 pathway. CONCLUSIONS: These results reveal a novel protective role for MPO during hypoxic stress, where it functions to moderate the innate immune response and limit collateral tissue damage in the liverspleen axis. The study provides new insights into the complex immunomodulatory functions of MPO and suggests its activity is essential for maintaining immune homeostasis during acute hypoxia.

Key Findings

• MPO deficiency exacerbates liver-spleen axis injury under hypoxic conditions.
• MPO-/- mice show increased phagocyte recruitment and elevated proinflammatory mediators (TNFα, IL1β, IL17A).
• MPO absence dysregulates the antioxidant response via the NRF2/HO1 pathway and increases NFκB, NLRP3, and iNOS expression.

Clinical Significance

Citation

Li Yonggui, Liu Xiaoli, Zhang Lingminget al.. Myeloperoxidase regulates hypoxia-induced inflammation and oxidative stress in liver-spleen axis. Journal of inflammation (London, England). 2026-May-02.