IL-11 ameliorates oxidative stress damage in neurons after spinal cord injury by activating the JAK/STAT signaling pathway

  • Int Immunopharmacol. 2023 Dec 30:127:111367. doi: 10.1016/j.intimp.2023.111367.
Yang Sun  1 ,  Xue Song  2 ,  Zhijun Geng  2 ,  Yibo Xu  3 ,  Linyu Xiao  4 ,  Yue Chen  4 ,  Bohan Li  3 ,  Jinran Shi  3 ,  Lian Wang  5 ,  Yueyue Wang  6 ,  Xiaofeng Zhang  2 ,  Lugen Zuo  5 ,  Jing Li  6 ,  Hezuo Lü  7 ,  Jianguo Hu  8
Affiliations
  • 1. Department of rehabilitation medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
  • 2. Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China.
  • 3. Bengbu Medical University, Bengbu, China.
  • 4. Department of rehabilitation medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Bengbu Medical University, Bengbu, China.
  • 5. Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
  • 6. Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
  • 7. Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China. Electronic address: [email protected].
  • 8. Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu, China; Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China. Electronic address: [email protected].
PMID: 38160564 DOI: 10.1016/j.intimp.2023.111367
Abstract

Objective: Excess Reactive Oxygen Species (ROS) generated by oxidative stress is a crucial factor affecting neuronal dysfunction after spinal cord injury (SCI). IL-11 has been reported to have antioxidative stress capacity. In the present study, we investigated the protective effect and mechanism of IL-11 against neuronal cell damage caused by oxidative imbalance.

Methods: We established a H2O2-induced oxidative stress injury model in PC12 cells and observed the effects of IL-11 on cellular activity, morphology, oxidase and antioxidant Enzymes, and ROS release. Furthermore, the effect of IL-11 on Apoptosis of PC12 cells was assessed by flow cytometry, a TUNEL assay and Western blotting. Transcriptome analysis and rescue experiments revealed the mechanism by which IL-11 protects neurons from oxidative stress damage. For the in vivo investigation, an adenovirus-mediated IL-11 overexpression SCI rat model was constructed to validate the beneficial effect of IL-11 against SCI.

Results: IL-11 significantly improved the viability and enhanced the antioxidant activity of H2O2-treated PC12 cells while reducing ROS release. In addition, IL-11 reduced H2O2-induced PC12 cell Apoptosis. Transcriptome analysis revealed that the JAK/STAT pathway may be related to the antioxidant activity of IL-11. Treatment with a JAK/STAT Inhibitor (Stattic) exacerbated the oxidative damage induced by H2O2 and attenuated the protective effects of IL-11. The results of in vivo studies showed that IL-11 prevented neuronal Apoptosis due to oxidative imbalance and promoted the restoration of motor function in SCI rats by activating the JAK/STAT signaling pathway.

Conclusion: IL-11 inhibited oxidative stress-induced neuronal Apoptosis at least in part by activating the JAK/STAT signaling pathway and further promoted the recovery of motor function. These findings suggest that IL-11 may be an effective target for the treatment for SCI.

Keywords
Apoptosis; Interleukin 11; JAK/STAT; Neuron; Oxidative damage; Spinal cord injury.
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