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-1β, 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.

中文翻译：

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Hemeoxygenase-1 通过抑制 M1 极化来增加细胞内铁储存并抑制巨噬细胞的炎症反应。

血红素加氧酶-1 (HO-1) 催化血红素降解的第一个限速酶步骤，产生一氧化碳、胆绿素和游离铁。大多数铁是通过血红素的分解从老化的红细胞中产生的，这主要发生在巨噬细胞中。然而，HO-1对铁代谢和巨噬细胞功能的作用尚不清楚。本研究探讨HO-1对巨噬细胞铁代谢的影响，探讨HO-1对巨噬细胞炎症反应、极化和迁移的作用。每4 d向C57BL/6 J小鼠静脉注射HO-1诱导剂血红素或HO-1抑制剂锌原卟啉，持续28 d。我们发现HO-1主要位于小鼠脾脏巨噬细胞的细胞质中。Hemin 激活 HO-1 显着增加脾脏中的铁沉积，上调铁蛋白和铁转运蛋白的基因表达，并下调二价金属转运蛋白 1 和铁调素的基因表达。Hemin处理诱导的HO-1增加了巨噬细胞的细胞内铁水平，减慢了细胞外铁的吸收，并加速了细胞内铁的排泄。此外，HO-1的激活显着降低了促炎细胞因子的表达，包括白细胞介素（IL）-6、IL-1β和诱导型一氧化氮合酶，但增加了抗炎细胞因子如IL-10的表达。此外，HO-1的激活抑制了巨噬细胞的M1型极化，并增加了巨噬细胞的迁移率。这项研究表明HO-1能够调节铁代谢、发挥抗炎作用并抑制巨噬细胞极化为M1型。