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

文献类型： 外文期刊

作者： Tang, Xueyou 1 ; Li, Yunqin 2 ; Zhao, Jing 1 ; Liang, Li 1 ; Zhang, Kang 1 ; Zhang, Xiaofeng 3 ; Yu, Hong 4 ; Du, Huahua 1 ;

作者机构： 1.Zhejiang Univ, Coll Anim Sci, MoE Key Lab Mol Anim Nutr, Minist Educ, Hangzhou 310058, Peoples R China

2.Zhejiang Univ, Anal Ctr Agrobiol & Environm Sci, Hangzhou 310058, Peoples R China

3.Zhejiang Acad Agr Sci, Inst Anim Husb & Vet Sci, Hangzhou 310004, Peoples R China

4.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou 310016, Zhejiang, Peoples R China

5.Zhejiang Univ, Coll Anim Sci, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China

关键词： Hemin; HO-1; inflammatory response; iron metabolism; macrophage polarization; macrophages

期刊名称：METALLOMICS （ 影响因子：3.4； 五年影响因子：4.2 ）

ISSN： 1756-5901

年卷期： 2023 年 15 卷 10 期

页码：

收录情况： SCI

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

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