Heme protects intestinal mucosal barrier in DSS-induced colitis through regulating macrophage polarization in both HO-1-dependent and HO-1-independent way
Heme protects intestinal mucosal barrier in DSS-induced colitis through regulating macrophage polarization in both HO-1-dependent and HO-1-independent way
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血红素通过 HO-1 依赖和 HO-1 独立方式调节巨噬细胞极化，保护 DSS 诱导的结肠炎中的肠粘膜屏障
DOI：
10.1096/fj.202000313rr
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发表时间：
2020-04-17
期刊：
影响因子：
4.8
通讯作者：
Tang, Wei
中科院分区：
文献类型：
--
作者：
Wu, Yanwei;Wu, Bing;Tang, Wei
据报道，血红蛋白衍生的血红素通过调节巨噬细胞朝向恢复在出血性疾病中发挥保护作用。黏膜出血是炎症性肠病（IBD）的病理特征之一。然而，尚不清楚血红素是否在巨噬细胞中提供抗炎特性，从而有助于肠粘膜屏障保护。在目前的研究中，我们研究了血红素对DSS诱导的结肠炎小鼠的有益作用，并探讨了潜在的机制。在体内，通过注射氯化血红素全身补充血红素减轻肠道炎症，并通过纠正异常的肠道巨噬细胞极化来修复肠粘膜屏障损伤。在体外实验中，我们证实了氯化血红素对BMDM的M1/M2巨噬细胞极化的相互调节作用。令人感兴趣的是，随着HO-1的敲低，氯高铁血红素对M1极化的抑制作用得以维持，而对M2极化的促进作用则被逆转。进一步的研究表明，氯化血红素通过Spi-C依赖的方式破坏IRF 5-NF-κ B p65复合物的形成，抑制NF-κ B p65的转位，从而抑制巨噬细胞的炎症反应。综上所述，这些结果表明，通过补充血红素来改变结肠组织微环境，通过以HO-1依赖性和HO-1非依赖性方式调节巨噬细胞极化，在DSS诱导的结肠炎小鼠中发挥保护作用，指示治疗性调节巨噬细胞功能和预防IBD的新选择。
Hemoglobin-derived heme was reported to play protective roles in hemorrhagic diseases by modulating the macrophages toward recovery. Mucosal bleeding is one of the pathological features of inflammatory bowel diseases (IBD). However, whether heme provides anti-inflammatory profiles in macrophages, thus contributing to the intestinal mucosal barrier protection, is unclear. In the current study, we investigated the beneficial effects of heme on DSS-induced colitis mice and explored the underlying mechanisms. In vivo, systemic heme supplementation by hemin injection relieved intestinal inflammation and remedied intestinal mucosal barrier damage by correcting abnormal intestinal macrophage polarization. In vitro, we confirmed the reciprocally regulating effects of hemin on M1/M2 macrophage polarization in BMDM. Intriguingly, with knockdown of HO-1, the inhibiting effects of hemin on M1 polarization were maintained, while the promoting effects on M2 polarization were reversed. Further research proved that hemin repressed the inflammatory profiles in macrophages through inhibiting the translocation of NF-kappa B p65 by disrupting IRF5-NF-kappa B p65 complex formation in Spi-C-dependent way. In conclusion, these results showed that the modification of colon tissue microenvironment with heme supplementation plays a protective role in DSS-induced colitis mice through regulating the macrophage polarization in both HO-1-dependent and HO-1-independent way, indicating a new choice to therapeutically modulate the macrophage function and prevent IBD.