Advances in the molecular mechanisms of NLRP3 inflammasome activators and inactivators

Dongling Liu; Xiang Zeng; Xiao Li; Chaochu Cui; Ruanling Hou; Zhikun Guo; Jawahar L Mehta; Xianwei Wang

doi:10.1016/j.bcp.2020.113863

Advances in the molecular mechanisms of NLRP3 inflammasome activators and inactivators

Biochem Pharmacol. 2020 May:175:113863. doi: 10.1016/j.bcp.2020.113863. Epub 2020 Feb 17.

Authors

Dongling Liu¹, Xiang Zeng², Xiao Li³, Chaochu Cui³, Ruanling Hou⁴, Zhikun Guo³, Jawahar L Mehta⁵, Xianwei Wang⁶

Affiliations

¹ Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: liudongling@xxmu.edu.cn.
² Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 510632, Guangdong, China.
³ Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China.
⁴ Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
⁵ Division of Cardiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
⁶ Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: 161042@xxmu.edu.cn.

PMID: 32081791
DOI: 10.1016/j.bcp.2020.113863

Abstract

NLRP3 inflammasome is an intracellular protein complex that initiates cellular injury via assembly of NLRP3, ASC and caspase-1 in response to microbial infection and sterile stressors. The importance of NLRP3 inflammasome in immunity and human diseases has been well documented. Up to now, targeted inhibition of the assembly of NLRP3 inflammasome complex and of its activation was thought to be therapeutic strategy for associated diseases. Recent studies show that a host of molecules such as NIMA-related kinase 7 (Nek7) and DEAD-box helicase 3 X-linked (DDX3X) and a large number of biological mediators including cytokines, microRNAs, nitric oxide, carbon monoxide, nuclear factor erythroid-2 related factor 2 (Nrf2) and cellular autophagy participate in the activation and inactivation of NLRP3 inflammasome. This review summarizes current understanding of the molecular basis of NLRP3 inflammasome activation and inactivation. This knowledge may lead to development of new therapies directed at NLRP3 inflammasome related diseases.

Keywords: DEAD-box helicase 3 X-linked; Interleukin-1β; NIMA-related kinase 7; NLRP3 inflammasome; Therapeutic target.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Autophagy / immunology
Cytokines / metabolism
DEAD-box RNA Helicases / metabolism
Humans
Inflammasomes / metabolism*
Inflammation / metabolism*
Inflammation / pathology
NF-E2-Related Factor 2 / metabolism
NIMA-Related Kinases / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Nitric Oxide / metabolism
Protein Processing, Post-Translational*

Substances

Cytokines
Inflammasomes
NF-E2-Related Factor 2
NFE2L2 protein, human
NLR Family, Pyrin Domain-Containing 3 Protein
Nitric Oxide
NEK7 protein, human
NIMA-Related Kinases
DDX3X protein, human
DEAD-box RNA Helicases