Background
Hemin chloride, a substrate of heme oxygenase (HO)-1, induces HO-1 expression on a variety of cells to exert anti-oxidant and anti-inflammatory roles.
A dramatic reduction of cell-associated M. hyorhinis DNA in a dose-dependent manner, with > 90% inhibition at 100 μm Hemin chloride. Hemin chloride treatment profoundly inhibited intracellular M. hyorhinis DNA levels within 10 h to nearly undetectable levels after 48 h[1]. Macrophage exposed to Hemin chloride exhibits modulation of non-opsonic phagocytosis of aged RBCs, ability to kill bacteria and secretion of cytokines.Translocation and sequestration of CD36 within the intracellular storage in the Hemin chloride treated macrophages. It in-turn modulates the global cytokine secretion from macrophages. CD36 has strong affinity for Hemin chloride with a dissociation constant of 1.26 ±0.24 μM[3]. Hemin chloride treatment decreased cell proliferation to 62.5 %, 51.3 %, and 38.8 % in PA-TU-8902, BxPC-3 and MiaPaCa-2 cancer cells, respectively. Enhancement of anti-proliferative effects of statins by Hemin chloride, documented as decreased cell proliferation after 48 h of co-treatment[5]. The presence of Hemin chloride in irradiated lung cancer cells enhanced the productivity of initial ROS, resulting in lipid peroxidation and subsequent ferroptosis[6].
In HDM-induced asthmatic mouse model, Hemin chloride-DCEVs inhalation reduced eosinophils infiltration and mucus secretion in the airway, decreased the levels of IL-4, IL-5, and IL-13 in the lung and the number of Th2 cells in mediastinal lymph nodes (MLNs), and increased the number of Treg cells in MLNs[2]. Hemin chloride-preconditioned mice exhibited preserved renal cell function, and the tubular injury score at 72h indicated that tubular damage was prevented[4]. When compared with wild-type littermates, the mortality for SS Cttn+/- mice trended to be lower after Hemin chloride infusion and these mice exhibited less severe lung injury and less necroptotic cell death[7].
参考文献:
[1]. Huang H, Dabrazhynetskaya A, et,al.Hemin chloride activation abrogates Mycoplasma hyorhinis replication in chronically infected prostate cancer cells via heme oxygenase-1 induction. FEBS Open Bio. 2021 Oct;11(10):2727-2739. doi: 10.1002/2211-5463.13271. Epub 2021 Sep 9. PMID: 34375508; PMCID: PMC8487054.
[2]. Wu Y, Yu Q, et,al.Hemin chloride-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles. J Leukoc Biol. 2022 Apr;111(4):837-848. doi: 10.1002/JLB.3A0321-175R. Epub 2021 Jul 23. PMID: 34296788; PMCID: PMC9292814.
[3]. Banesh S, Layek S, et,al. Hemin chloride acts as CD36 ligand to activate down-stream signalling to disturb immune responses and cytokine secretion from macrophages. Immunol Lett. 2022 Mar;243:1-18. doi: 10.1016/j.imlet.2022.01.004. Epub 2022 Jan 31. PMID: 35104496.
[4]. Chen HH, Lu PJ, et,al. Heme oxygenase-1 ameliorates kidney ischemia-reperfusion injury in mice through extracellular signal-regulated kinase 1/2-enhanced tubular epithelium proliferation. Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2195-201. doi: 10.1016/j.bbadis.2015.07.018. Epub 2015 Jul 30. PMID: 26232688.
[5]. Vanova K, Boukalova S, et,al. Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells. BMC Cancer. 2016 May 12;16:309. doi: 10.1186/s12885-016-2343-9. PMID: 27175805; PMCID: PMC4866069.
[6]. Almahi WA, Yu KN, et,al. Hemin chloride enhances radiosensitivity of lung cancer cells through ferroptosis. Exp Cell Res. 2022 Jan 1;410(1):112946. doi: 10.1016/j.yexcr.2021.112946. Epub 2021 Nov 24. PMID: 34826424.
[7]. Jones NM, Sysol JR,et,al. Cortactin loss protects against Hemin chloride-induced acute lung injury in sickle cell disease. Am J Physiol Lung Cell Mol Physiol. 2022 Jun 1;322(6):L890-L897. doi: 10.1152/ajplung.00274.2021. Epub 2022 May 3. PMID: 35503995; PMCID: PMC9169831.
氯化血红素是血红素加氧酶(HO)-1的底物，可诱导多种细胞表达HO-1，发挥抗氧化和抗炎作用。
细胞相关的猪鼻支原体 DNA 以剂量依赖性方式显着减少，>；在 100 μm 氯化血红素下有 90% 的抑制。氯化血红素处理可在 10 小时内显着抑制细胞内猪鼻支原体 DNA 水平，48 小时后几乎检测不到[1]。暴露于氯化血红素的巨噬细胞表现出对老化红细胞的非调理吞噬作用的调节、杀灭细菌的能力和细胞因子的分泌。CD36 在氯化血红素处理的巨噬细胞的细胞内储存中的易位和隔离。它反过来调节巨噬细胞的整体细胞因子分泌。 CD36 对氯化血红素具有很强的亲和力，解离常数为 1.26 ±0.24 μM[3]。氯化血红素处理将 PA-TU-8902、BxPC-3 和 MiaPaCa-2 癌细胞的细胞增殖分别降低至 62.5%、51.3% 和 38.8%。氯化血红素增强他汀类药物的抗增殖作用，记录为联合治疗 48 小时后细胞增殖减少[5]。受照射的肺癌细胞中氯化血红素的存在增强了初始 ROS 的生产力，导致脂质过氧化和随后的铁死亡[6]。
在 HDM 诱导的哮喘小鼠模型中，氯化血红素-DCEVs 吸入减少了气道中的嗜酸性粒细胞浸润和粘液分泌，降低了肺中 IL-4、IL-5 和 IL-13 的水平以及 Th2 的数量纵隔淋巴结 (MLN) 中的细胞，并增加 MLN 中 Treg 细胞的数量[2]。氯化血红素预处理小鼠的肾细胞功能得到保护，72 小时的肾小管损伤评分表明肾小管损伤得到了预防[4]。与野生型同窝小鼠相比，SS Cttn+/- 小鼠在输注氯化血红素后死亡率趋于降低，并且这些小鼠表现出较轻的肺损伤和较少的坏死性细胞死亡[7]。
Protocol
| Cell experiment [1]: |
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Cell lines
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LNCaP cells
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Preparation Method
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Real-time PCR amplification of the total DNA from M. hyorhinis -infected LNCaP cells cultured for 48 h in the presence of varying concentrations of Hemin chloride.
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Reaction Conditions
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100 μM Hemin chloride for 48 h
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Applications
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Hemin chloride treatment induces HO-1 expression and inhibits M. hyorhinis replication in LNCaP prostate cancer cells.
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| Animal experiment [2]: |
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Animal models
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C57BL/6 mice
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Preparation Method
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House dust mite (HDM)-sensitized and challenged mice were instilled intranasally with 100 μg Hemin chloride-DCEVs at 1 d before sensitization and challenge.
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Dosage form
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100 μg Hemin chloride-DCEVs at 1day
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Applications
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In HDM-induced asthmatic mouse model, Hemin chloride-DCEVs inhalation reduced eosinophils infiltration and mucus secretion in the airway, decreased the levels of IL-4, IL-5, and IL-13 in the lung and the number of Th2 cells in mediastinal lymph nodes (MLNs), and increased the number of Treg cells in MLNs.
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参考文献:
[1]. Huang H, Dabrazhynetskaya A, et,al. Hemin chloride activation abrogates Mycoplasma hyorhinis replication in chronically infected prostate cancer cells via heme oxygenase-1 induction. FEBS Open Bio. 2021 Oct;11(10):2727-2739. doi: 10.1002/2211-5463.13271. Epub 2021 Sep 9. PMID: 34375508; PMCID: PMC8487054.
[2].Wu Y, Yu Q, et,al. Hemin chloride-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles. J Leukoc Biol. 2022 Apr;111(4):837-848. doi: 10.1002/JLB.3A0321-175R. Epub 2021 Jul 23. PMID: 34296788; PMCID: PMC9292814.
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