title: Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome.
abstract: Inflammasomes are involved in diverse inflammatory diseases, so the activation of inflammasomes needs to be tightly controlled to prevent excessive inflammation. However, the endogenous regulatory mechanisms of inflammasome activation are still unclear. Here, we report that the neurotransmitter dopamine (DA) inhibits NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). DRD1 signaling negatively regulates NLRP3 inflammasome via a second messenger cyclic adenosine monophosphate (cAMP), which binds to NLRP3 and promotes its ubiquitination and degradation via the E3 ubiquitin ligase MARCH7. Importantly, in vivo data show that DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation, including neurotoxin-induced neuroinflammation, LPS-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation. Taken together, our results reveal an endogenous mechanism of inflammasome regulation and suggest DRD1 as a potential target for the treatment of NLRP3 inflammasome-driven diseases.
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xiaqiong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing 102206, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ding
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China; Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China. Electronic address: tzg@ustc.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China; Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China. Electronic address: zrb1980@ustc.edu.cn.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D058847:Inflammasomes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018377:Neurotransmitter Agents / Q000378:metabolism*; D066329:Protein Aggregates; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D002352:Carrier Proteins; C583260:DRD1 protein, human; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018377:Neurotransmitter Agents; C492716:Nlrp3 protein, mouse; D066329:Protein Aggregates; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D004298:Dopamine