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Cell Death Differ. 2019 Jan;26(1):130-145. doi: 10.1038/s41418-018-0105-8. Epub 2018 Apr 17.

lincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation.

Author information

1
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China.
2
Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
3
Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China. rxzhang@tmu.edu.cn.
4
Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, China. rxzhang@tmu.edu.cn.

Abstract

Inflammasome activation plays key roles in host defense, but also contributes to the pathogenesis of auto-inflammatory, and neurodegenerative diseases. As autophagy is connected with both the innate and adaptive immune systems, autophagic dysfunction is also closely related to inflammation, infection, and neurodegeneration. Here we identify that lincRNA-Cox2, previously known as a mediator of both the activation and repression of immune genes expression in innate immune cells, could bind NF-κB p65 and promote its nuclear translocation and transcription, modulating the expression of inflammasome sensor NLRP3 and adaptor ASC. Knockdown of lincRNA-Cox2 inhibited the inflammasome activation and prevented the lincRNA-Cox2-triggered caspase-1 activation, leading to decreased IL-1β secretion and weakened TIR-domain-containing adapter-inducing interferon-β (TRIF) cleavage, thereby enhancing TRIF-mediated autophagy. Elucidation of the link between lincRNA-Cox2 and the inflammasome-autophagy crosstalk in macrophage and microglia reveals a role for lncRNAs in activation of NLRP3 inflammasome and autophagy, and provides new opportunities for therapeutic intervention in neuroinflammation-dependent diseases.

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