Heme oxygenase-1 increases intracellular iron storage and suppresses inflammatory response of macrophages by inhibiting M1 polarization

• DOI: 10.1093/mtomcs/mfad062
• Publication Date: 2023-10-15T01:18:34Z
• Authors: Xueyou Tang; Yunqin Li; Jing Zhao; Li Liang; Kang Zhang; Xiaofeng Zhang; Hong Yu; Huahua Du
• Keywords: Hemin; Ferroportin; Proinflammatory cytokine; HMOX1; Macrophage polarization; Biliverdin; DMT1

Abstract Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation, producing carbon monoxide, biliverdin, free iron. Most iron is derived from aged erythrocytes by decomposition heme, which happened mainly in macrophages. However, role HO-1 on metabolism function macrophage unclear. The present study investigated effect macrophages, explored inflammatory response, polarization, migration inducer Hemin or inhibitor zinc protoporphyrin was intravenously injected to C57BL/6 J mice every 4 d for 28 d. We found that located cytoplasm splenic macrophages mice. Activation significantly increased deposition spleen, up-regulated gene expression ferritin ferroportin, down-regulated divalent metal transporter 1 hepcidin. Induced treatment intracellular levels slowed down absorption extracellular iron, accelerated excretion In addition, activation decreased pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, inducible nitric oxide synthase, but anti-inflammatory such as IL-10. Furthermore, inhibited M1-type rate This demonstrated able regulate metabolism, exert effects, inhibit polarization M1 type.