PMID- 37206550
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230522
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Print)
IS  - 1792-0981 (Linking)
VI  - 25
IP  - 6
DP  - 2023 Jun
TI  - IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via 
      the NRF2 pathway.
PG  - 289
LID - 10.3892/etm.2023.11988 [doi]
LID - 289
AB  - 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-1beta 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.
CI  - Copyright: (c) Xu et al.
FAU - Xu, Jinmei
AU  - Xu J
AD  - Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Han, Xu
AU  - Han X
AD  - Medical Laboratory, Harbin Medical University, Daqing, Heilongjiang 163001, P.R. 
      China.
FAU - Xia, Nan
AU  - Xia N
AD  - Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Zhao, Qingsong
AU  - Zhao Q
AD  - Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Cheng, Zhifeng
AU  - Cheng Z
AD  - Department of Endocrinology, Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230503
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC10189585
OTO - NOTNLM
OT  - IL-37
OT  - atherosclerosis
OT  - ferroptosis
OT  - novel inflammatory factors
OT  - oxidative stress
COIS- The authors declare that they have no competing interests.
EDAT- 2023/05/19 19:15
MHDA- 2023/05/19 19:16
PMCR- 2023/05/03
CRDT- 2023/05/19 15:42
PHST- 2022/11/22 00:00 [received]
PHST- 2023/03/16 00:00 [accepted]
PHST- 2023/05/19 19:16 [medline]
PHST- 2023/05/19 19:15 [pubmed]
PHST- 2023/05/19 15:42 [entrez]
PHST- 2023/05/03 00:00 [pmc-release]
AID - ETM-25-6-11988 [pii]
AID - 10.3892/etm.2023.11988 [doi]
PST - epublish
SO  - Exp Ther Med. 2023 May 3;25(6):289. doi: 10.3892/etm.2023.11988. eCollection 2023 
      Jun.