Open Access

IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway

  • Authors:
    • Jinmei Xu
    • Xu Han
    • Nan Xia
    • Qingsong Zhao
    • Zhifeng Cheng
  • View Affiliations

  • Published online on: May 3, 2023     https://doi.org/10.3892/etm.2023.11988
  • Article Number: 289
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

IL‑37 is a newly discovered inflammatory factor. However, the protective effect and underlying mechanisms of IL‑37 on atherosclerosis remain unclear. In the present study, IL‑37 was used for intraperitoneal injection in diabetic ApoE‑/‑ mice caused by streptozotocin. High glucose (HG)/ox‑LDL was used to stimulate THP‑1 original macrophage followed by IL‑37 pretreatment in vitro. The atheromatous plaque area, oxidative stress and inflammation levels in ApoE‑/‑ mice were evaluated, and the level of macrophage ferroptosis was detected in vivo and in vitro. It was identified that IL‑37 treatment significantly decreased plaque area in diabetic ApoE‑/‑ mice. IL‑37 not only improved blood lipid levels in mice, but also reduced serum levels of inflammatory factors including IL‑1β and IL‑18. Furthermore, IL‑37 increased GPX4 and nuclear factor erythroid 2‑related factor 2 (NRF2) in the aorta of diabetic mice. In vitro experiment revealed that IL‑37 inhibited HG/ox‑LDL‑induced ferroptosis in macrophages, as evidenced by improved cell membrane oxidation, reduced malondialdehyde production and increased GPX4 expression. Moreover, it was also found that IL‑37 enhanced the nuclear translocation of NRF2 in macrophages, while ML385, a specific NRF2 inhibitor, significantly attenuated the protective effect of IL‑37 on macrophage ferroptosis caused by HG/ox‑LDL. In conclusion, IL‑37 suppressed macrophage ferroptosis to attenuate atherosclerosis progression via activating the NRF2 pathway.
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June-2023
Volume 25 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Xu J, Han X, Xia N, Zhao Q and Cheng Z: IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway. Exp Ther Med 25: 289, 2023
APA
Xu, J., Han, X., Xia, N., Zhao, Q., & Cheng, Z. (2023). IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway. Experimental and Therapeutic Medicine, 25, 289. https://doi.org/10.3892/etm.2023.11988
MLA
Xu, J., Han, X., Xia, N., Zhao, Q., Cheng, Z."IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway". Experimental and Therapeutic Medicine 25.6 (2023): 289.
Chicago
Xu, J., Han, X., Xia, N., Zhao, Q., Cheng, Z."IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway". Experimental and Therapeutic Medicine 25, no. 6 (2023): 289. https://doi.org/10.3892/etm.2023.11988