M1/M2 Macrophages in Diabetic Nephropathy: Nrf2/HO-1 as Therapeutic Targets

Current Pharmaceutical Design
Robert C LandisAndre R Greenidge

Abstract

The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the latter phase is controlled by alternatively activated macrophages (M2) to resolve inflammation and promote tissue remodelling with the release of growth factors. In a simple human inflammatory response, such as acute crystal arthropathy, macrophages progress linearly through M1 and M2 phases; however, in chronic inflammatory responses, such as atherosclerosis and Diabetic Nephropathy (DN), both M1 and M2 macrophages may coexist, leading to persistent inflammation and fibrosis. A key macrophage receptor that regulates conversion from M1 to M2 is CD163, the hemoglobin scavenger receptor. Scavenging of hemoglobin:haptoglobin (Hb:Hp) complexes via CD163 leads to nuclear translocation of the transcription factor Nrf2 (NF-E2-related factor 2), upregulation of heme oxygenase (HO)-1 cytoprotective protein, and release of interleukin (IL)-10 anti-inflammatory cytokine; IL-10 is then linked in a positive feedback loop to further CD163 expression. The potency of this M1/M2 switching pathway...Continue Reading

Citations

Mar 7, 2020·Journal of Zhejiang University. Science. B·Zhi-Feng ZhouJin-Lei Lv
Jan 19, 2020·Scientific Reports·Stephan DreschersThorsten W Orlikowsky
Jul 13, 2019·International Journal of Molecular Sciences·Keiichiro MatobaRimei Nishimura
Jun 4, 2020·Experimental Biology and Medicine·Liliany Souza de Brito AmaralTelma de Jesus Soares
Feb 12, 2021·Frontiers in Cell and Developmental Biology·Hong ZhouLi-Qin Tang
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Nov 6, 2020·Cellular Signalling·Karl-Friedrich Beck, Josef Pfeilschifter
Aug 22, 2021·Antioxidants & Redox Signaling·Mihály BaloghAndrew J Shepherd

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