Heme protects intestinal mucosal barrier in DSS-induced colitis through regulating macrophage polarization in both HO-1-dependent and HO-1-independent way
| Autor: | Heng Li, Bing Wu, Chunlan Feng, Huimin Lu, Jianping Zuo, Qing Qi, Chen Fan, Yuanzhuo Gao, Wei Tang, Zongwang Zhang, Yanwei Wu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Colon Macrophage polarization Anti-Inflammatory Agents Heme Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo Genetics medicine Animals Colitis Intestinal Mucosa Molecular Biology Inflammation Gene knockdown Macrophages Dextran Sulfate Transcription Factor RelA Membrane Proteins Macrophage Activation medicine.disease M2 Macrophage Inflammatory Bowel Diseases Ulcerative colitis Cell biology Mice Inbred C57BL 030104 developmental biology chemistry Interferon Regulatory Factors Cytokines Female Inflammation Mediators 030217 neurology & neurosurgery Heme Oxygenase-1 Biotechnology Hemin |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(6) |
| ISSN: | 1530-6860 |
| Popis: | 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-κB p65 by disrupting IRF5-NF-κB 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. |
| Databáze: | OpenAIRE |
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