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Transient receptor potential vanilloid 4 is a critical mediator in LPS mediated inflammation by mediating calcineurin/NFATc3 signaling.
Li, Min; Fang, Xiang-Zhi; Zheng, Yong-Feng; Xie, Yun-Bin; Ma, Xiao-Dong; Liu, Xiao-Tian; Xia, Yan; Shao, Dong-Hua.
Afiliación
  • Li M; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Fang XZ; Department of Anesthesiology, Subei People's Hospital, YangZhou, 225001, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zheng YF; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Xie YB; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Ma XD; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Liu XT; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Xia Y; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China.
  • Shao DH; Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, ZhengJang, 212002, China. Electronic address: 13805281211@163.com.
Biochem Biophys Res Commun ; 513(4): 1005-1012, 2019 06 11.
Article en En | MEDLINE | ID: mdl-31005256
Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is thought to be an essential component of inflammatory response. However, its role and mechanism in regulating acute lung injury (ALI) and macrophages activation are not well characterized. In our study, we observe that blockade of TRPV4 using GSK2193874 or HC-067047 greatly improve the pneumonedema, the lung pathologic changes, the up-regulation of proinflammatory cytokines and the neutrophil infiltration in LPS-induced lung injury. In vitro, knockdown of TRPV4 in macrophages reduces the levels of pro-inflammatory cytokines, ROS production, Ca2+ concentration in cytoplasma and the activation of calcineurin/NFATc3 signaling. Importantly, change of extracellular Ca2+ in culture medium prevents LPS-induced NFATc3 nuclear translocation, up-regulation of proinflammatory cytokines and ROS production in macrophages. Inhibition of calcineurin with cyclosporine A, FK506 down-regulates the levels of NFATc3 nuclear translocation and proinflammatory cytokines expression. Our results demonstrate that TRPV4-dependent Ca2+ influx contributes to LPS-induced macrophage activation by calcineurin-NFATc3 pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Calcineurina / Canales Catiónicos TRPV / Factores de Transcripción NFATC / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Calcineurina / Canales Catiónicos TRPV / Factores de Transcripción NFATC / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos