Parthenolide promotes the repair of spinal cord injury by modulating M1/M2 polarization via the NF-κB and STAT 1/3 signaling pathway

Cell Death Discovery - Tập 6 Số 1
Gaojian Tao1, Dingfei Qian2, Linwei Li3, Xiaowei Wang2, Zheng Zhou2, Wei Liu2, Tong Zhu4, Benxiang Ning4, Qian Yan-ning1, Wei Zhou2, Jian Chen2
1Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
3Department of Orthopedic, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China
4Department of Pain Management, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China

Tóm tắt

AbstractSpinal cord injury (SCI) is a severe neurological disease; however, there is no effective treatment for spinal cord injury. Neuroinflammation involves the activation of resident microglia and the infiltration of macrophages is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Parthenolide (PN) has been reported to exert anti-inflammatory effects in fever, migraines, arthritis, and superficial inflammation; however, the role of PN in SCI therapeutics has not been clarified. In this study, we showed that PN could improve the functional recovery of spinal cord in mice as revealed by increased BMS scores and decreased cavity of spinal cord injury in vivo. Immunofluorescence staining experiments confirmed that PN could promote axonal regeneration, increase myelin reconstitution, reduce chondroitin sulfate formation, inhibit scar hyperplasia, suppress the activation of A1 neurotoxic reactive astrocytes and facilitate shift from M1 to M2 polarization of microglia/macrophages. To verify how PN exerts its effects on microglia/macrophages polarization, we performed the mechanism study in vitro in microglia cell line BV-2. PN could significantly reduce M1 polarization in BV2 cells and partially rescue the decrease in the expression of M2 phenotype markers of microglia/macrophage induced by LPS, but no significant effect on M2 polarization stimulated with IL-4 was observed. Further study demonstrated PN inhibited NF-κB signal pathway directly or indirectly, and suppressed activation of signal transducer and activator of transcription 1 or 3 (STAT1/3) via reducing the expression of HDAC1 and subsequently increasing the levels of STAT1/3 acetylation. Overall, our study illustrated that PN may be a promising strategy for traumatic SCI.

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Tài liệu tham khảo

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Cell Death Discovery

Tập 6 Số 1

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