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The macrophage heme-heme oxygenase-1 system and its role in inflammation

机译:巨噬细胞血红素血红素酶-1系统及其在炎症中的作用

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摘要

Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO, plays a critical role in inflammation and iron homeostasis. Regulatory functions of HO -1 are mediated via the catalytic breakdown of heme, which is an iron-containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory effects. In addition, the HO reaction produces the antioxidant and anti-inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently converted into bilirubin, along with iron, which is reutilized for erythropoiesis. HO -1 is up-regulated by a plethora of stimuli and injuries in most cell types and tissues and provides salutary effects by restoring physiological homeostasis. Notably, HO -1 exhibits critical immuno-modulatory functions in macrophages, which are a major cell population of the mononuclear phagocyte system. Macrophages play key roles as sentinels and regulators of the immune system and HO -1 in these cells appears to be of critical importance for driving resolution of inflammatory responses. In this review, the complex functions and regulatory mechanisms of HO-1 in macrophages will be high-lighted. A particular focus will be the intricate interactions of HO -1 with its substrate heme, which play a contradictory role in distinct physiological and pathophysiological settings. The therapeutic potential of targeted modulation of the macrophage heme-HO-1 system will be discussed in the context of inflammatory disorders.
机译:血红素氧合酶(HO)-1,血红素降解酶HO的诱导型同种型,在炎症和铁稳态中起着关键作用。 HO -1的调节功能通过血红素的催化分解介导,其是一种含铁四吡咯配合物,具有潜在的促氧化剂和促炎作用。此外,HO反应产生抗氧化剂和抗炎化合物一氧化碳(CO)和Biliverdin,随后转化为胆红素,与铁一起转化为促红细胞的重新利用。 HO -1由大多数细胞类型和组织中的血液刺激和损伤是上调的,通过恢复生理稳态提供良好的效果。值得注意的是,HO -1在巨噬细胞上表现出关键的免疫调节功能,这是单核吞噬细胞系统的主要细胞群。巨噬细胞扮演关键作用作为免疫系统的哨兵和调节剂,这些细胞中的HO -1似乎对驱动炎症反应的分辨率至关重要。在本文中,HO-1在巨噬细胞中的复杂功能和调节机制将是高光线。特定的焦点将是HO -1与其底物血红素的复杂相互作用,其在不同的生理和病理生理环境中起着矛盾的作用。在炎症障碍的背景下将讨论巨噬细胞血红素HO-HO-1系统的靶向调节的治疗潜力。

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