2. Academic Validation
  3. TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia

TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia

  • Cell Death Dis. 2021 Dec 14;12(12):1159. doi: 10.1038/s41419-021-04450-9.
Yahui Zhang  # 1,  Baohua Hou  # 2,  Peiyu Liang 1,  Xin Lu 1,  Yifan Wu 1,  Xinyi Zhang 1,  Yuanteng Fan 3,  Yumin Liu 3,  Taoxiang Chen 4,  Wanhong Liu 5,  Biwen Peng 4,  Jun Yin 1,  Song Han 6,  Xiaohua He 7
Affiliations

Affiliations

  • 1 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • 2 Medical College, Henan Polytechnic University, Jiaozuo, China.
  • 3 Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China.
  • 4 Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
  • 6 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China. hansong@whu.edu.cn.
  • 7 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China. hexiaohua@whu.edu.cn.
  • # Contributed equally.
PMID: 34907173 DOI: 10.1038/s41419-021-04450-9
Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a CA2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating CA2+ influx and phosphorylation of Phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1-Ca2+-PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.

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