Effects of thioredoxin reductase 1 on ferroptosis and immune function of dendritic cells in septic mice

Zhou Qiyuan; Li Jingyan; Cao Yanmin; Li Weiling; Dong Ning; Wu Yao; Tian Yingping; Yao Yongming

doi:10.3760/cma.j.cn501225-20241118-00451

Volume 41 Issue 3

Mar. 2025

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Article Navigation > CHINESE JOURNAL OF BURNS AND WOUNDS > 2025 > 41(3): 212-221

Zhou QY,Li JY,Cao YM,et al.Effects of thioredoxin reductase 1 on ferroptosis and immune function of dendritic cells in septic mice[J].Chin J Burns Wounds,2025,41(3):212-221.DOI: 10.3760/cma.j.cn501225-20241118-00451.

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Effects of thioredoxin reductase 1 on ferroptosis and immune function of dendritic cells in septic mice

doi: 10.3760/cma.j.cn501225-20241118-00451

1.
Emergency Department, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
2.
Emergency Department, the Fourth Hospital of Shijiazhuang, Shijiazhuang 050000, China
3.
Medical Innovation Research Department and the Fourth Medical Center of PLA General Hospital, Beijing 100853, China

Funds:

Key Program of National Natural Science Foundation of China 82241062

Youth Science Fund Program of National Natural Science Foundation of China 82302412

Hebei Natural Science Foundation H2023206202

Beijing Municipal Natural Science Foundation 7244296

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Corresponding author: Tian Yingping, Email: tianyingping-jzh@163.com; Yao Yongming, Email: c_ff@sina.com
Received Date: 2024-11-18

Abstract

Abstract

Objective To investigate the effects of thioredoxin reductase 1 (TXNRD1) on ferroptosis and immune function of dendritic cells (DCs) in septic mice, and to provide a basis for improving the immunosuppression in sepsis caused by wound infection. Methods This study was an experimental research. Sixty male C57BL/6J mice aged 6-8 weeks were subjected to cecal ligation and puncture (CLP) to establish sepsis models. Ten mice were selected at 0 (immediately), 6, 12, 24, 48, and 72 h after CLP surgery, respectively, according to the random number table method. Mouse splenic DCs were isolated using CD11c-positive magnetic beads. The protein expressions of TXNRD1, and anti-ferroptosis proteins solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the cells were detected by Western blotting, the reduced glutathione (GSH) content in the cells was measured by colorimetric assay, the lipid peroxidation level was assessed via live-cell imaging technology, and the levels of major histocompatibility complex class Ⅱ subtype I-A/I-E and leukocyte differentiation antigens CD80 and CD86 were detected by flow cytometry. Another 100 male C57BL/6J mice aged 6-8 weeks were divided into corn oil+sham injury group, corn oil+CLP group, inhibitor+sham injury group, and inhibitor+CLP group according to the random number table method, with 25 mice in each group. Mice in the two inhibitor groups were intraperitoneally injected with TXNRD1 inhibitor auranofin, while mice in the two corn oil groups were intraperitoneally injected with corn oil. One hour later, mice in the two CLP groups underwent CLP surgery to establish sepsis models, while mice in the two sham injury groups underwent sham surgery. Twenty mice from each group were selected to observe survival within 7 d post-surgery, and the survival rate was calculated. At 24 h post-surgery, mouse splenic DCs from the remaining 5 mice in each group were collected for corresponding assays as above. Results Compared with those at 0 h after CLP surgery, the protein expressions of TXNRD1, GPX4, and SLC7A11 in mouse cells at 24 h after CLP surgery and the protein expression of TXNRD1 in mouse cells at 48 h after CLP surgery were significantly decreased (P<0.05), the GSH content in mouse cells was significantly decreased at 24 and 48 h after CLP surgery (P<0.05). The lipid peroxidation level in mouse cells was low at 0, 6, and 12 h after CLP surgery, slightly lower than that at 72 h after CLP surgery; the lipid peroxidation levels in mouse cells at 24 and 48 h after CLP surgery were significantly higher than those at 0, 6, 12, and 72 h after CLP surgery. Compared with those at 0 h after CLP surgery, the levels of I-A/I-E and CD80 in mouse cells at 6, 12, 24, 48, and 72 h after CLP surgery and the levels of CD86 in mouse cells at 12, 24, and 48 h after CLP surgery were significantly increased (P<0.05). At 24 h post-surgery, the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in corn oil+CLP group were significantly lower than those in corn oil+sham injury group (P<0.05), while the protein expressions of TXNRD1, SLC7A11, and GPX4 in mouse cells in inhibitor+CLP group were significantly lower than those in corn oil+CLP group and inhibitor+sham injury group (P<0.05). At 24 h post-surgery, the content of GSH in mouse cells in corn oil+CLP group was (239±32) μg/mg, which was significantly lower than (366±59) μg/mg in corn oil +sham injury group (P<0.05); the content of GSH in mouse cells in inhibitor+CLP group was (134±19) μg/mg, which was significantly lower than (355±31) μg/mg in inhibitor+sham injury group and that in corn oil+CLP group (with both P values<0.05). At 24 h post-surgery, the lipid peroxidation level of mouse cells in inhibitor+CLP group was significantly higher than that in the other three groups (P<0.05). At 24 h post-surgery, the levels of I-A/I-E, CD80, and CD86 in mouse cells in corn oil+CLP group were significantly higher than those in corn oil+sham injury group (P<0.05), while the levels of I-A/I-E and CD80 in mouse cells in inhibitor+CLP group were significantly higher than those in inhibitor+sham injury group (P<0.05) but significantly lower than those in corn oil+CLP group (P<0.05); the level of CD86 in mouse cells in inhibitor+sham injury group was significantly higher than that in corn oil+sham injury group (P<0.05). Within 7 d post-surgery, the survival rate of mice in inhibitor+CLP group was significantly lower than that in inhibitor+sham injury group and corn oil+CLP group (with χ² values of 31.19 and 3.91, respectively, both P values <0.05). Conclusions In septic mice, the expression of TXNRD1 in DCs is reduced, cell ferroptosis is enhanced, and immune function is weakened. The inhibition of TXNRD1 in DCs will exacerbate cell ferroptosis and immune function suppression, and is closely related to the poor prognosis of sepsis.
- Sepsis,
- Immunity,
- Dendritic cells,
- Oxidative stress,
- Ferroptosis,
- Thioredoxin reductase 1

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References

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