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Macrophage Nrf2, an anti-inflammatory signal in hepatic ischemia/reperfusion injury

Cellular & Molecular Immunology volume 20, pages 427–428 (2023)Cite this article

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Recently, the manuscript entitled Macrophage nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency promotes innate immune activation by tissue inhibitor of metalloproteinase 3 (Timp3)-mediated RhoA/ROCK pathway in the ischemic liver by Rao and colleagues in Hepatology 2022, vol. 75 [1] described a novel role of Nrf2 in innate immunity in response to hepatic ischemia/reperfusion injury (IRI). Nrf2 is generally considered a redox signaling controller and drives protective signals as an antioxidant gene in multiple organs and diseases. Rao et al. discovered that independent of its antioxidant activity, Nrf2 in macrophages directly mediates anti-inflammatory signaling and plays an essential role in prevention of IRI.

Hepatic IRI is a severe complication of liver transplantation and hepatectomy operations. It is characterized by intensive hepatocyte damage and inflammatory cell infiltration. Oxidative stress and innate immune responses are essential pathogenic factors. However, its pathophysiologic mechanisms at the molecular and cellular levels are not fully understood.

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References

  1. Rao J, Qiu J, Ni M, Wang H, Wang P, Zhang L, et al. Macrophage nuclear factor erythroid 2-related factor 2 deficiency promotes innate immune activation by tissue inhibitor of metalloproteinase 3-mediated RhoA/ROCK pathway in the ischemic liver. Hepatology. 2022;75:1429–45. https://doi.org/10.1002/hep.32184

    Article  CAS  PubMed  Google Scholar 

  2. Saha S, Buttari B, Panieri E, Profumo E, Saso L. An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation. Molecules. 2020;25:5474. https://doi.org/10.3390/molecules25225474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mohs A, Otto T, Schneider KM, Peltzer M, Boekschoten M, Holland CH, et al. Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis. J Hepatol. 2021;74:638–48. https://doi.org/10.1016/j.jhep.2020.09.037

    Article  CAS  PubMed  Google Scholar 

  4. Li L, Fu J, Liu D, Sun J, Hou Y, Chen C, et al. Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARgamma expression. Redox Biol. 2020;30:101412. https://doi.org/10.1016/j.redox.2019.101412

    Article  CAS  PubMed  Google Scholar 

  5. Sun J, Fu J, Li L, Chen C, Wang H, Hou Y, et al. Nrf2 in alcoholic liver disease. Toxicol Appl Pharm. 2018;357:62–69. https://doi.org/10.1016/j.taap.2018.08.019

    Article  CAS  Google Scholar 

  6. Ke B, Shen XD, Zhang Y, Ji H, Gao F, Yue S, et al. KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver transplants. J Hepatol. 2013;59:1200–7. https://doi.org/10.1016/j.jhep.2013.07.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun. 2016;7:11624. https://doi.org/10.1038/ncomms11624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Casagrande V, Mauriello A, Bischetti S, Mavilio M, Federici M, Menghini R. Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma. Sci Rep. 2017;7:6747. https://doi.org/10.1038/s41598-017-06439-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Azar F, Courtet K, Dekky B, Bonnier D, Dameron O, Colige A, et al. Integration of miRNA-regulatory networks in hepatic stellate cells identifies TIMP3 as a key factor in chronic liver disease. Liver Int. 2020;40:2021–33. https://doi.org/10.1111/liv.14476

    Article  CAS  PubMed  Google Scholar 

  10. Tang ZY, Loss G, Carmody I, Cohen AJ. TIMP-3 ameliorates hepatic ischemia/reperfusion injury through inhibition of tumor necrosis factor-alpha-converting enzyme activity in rats. Transplantation. 2006;82:1518–23. https://doi.org/10.1097/01.tp.0000243381.41777.c7

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Molecular Biosciences, UC Davis, Rm. 3009, 1089 Veterinary Medicine Dr., Davis, CA, 95616, US

    Joy X. Jiang

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  1. Joy X. Jiang
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Correspondence to Joy X. Jiang.

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Jiang, J.X. Macrophage Nrf2, an anti-inflammatory signal in hepatic ischemia/reperfusion injury. Cell Mol Immunol 20, 427–428 (2023). https://doi.org/10.1038/s41423-022-00964-0

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