title: Liver X receptors agonists suppress NLRP3 inflammasome activation.
abstract: Inflammasomes are multiprotein complexes that control the production of IL-1β and IL-18. NLRP3 inflammasome, the most characterized inflammasome, plays prominent roles in defense against infection, however aberrant activation is deleterious and leads to diseases. Therefore, its tight control offers therapeutic promise. Liver X receptors (LXRs) have significant anti-inflammatory properties. Whether LXRs regulate inflammasome remains unresolved. We thus tested the hypothesis that LXR's anti-inflammatory properties may result from its ability to suppress inflammasome activation. In this study, LXRs agonists inhibited the induction of IL-1β production, caspase-1 cleavage and ASC oligomerization by NLRP3 inflammasome. The agonists also inhibited inflammasome-associated mtROS production. Importantly, the agonists inhibited the priming of inflammasome activation. In vivo data also showed that LXRs agonist prevented NLRP3-dependent peritonitis. In conclusion, LXRs agonists are identified to potently suppress NLRP3 inflammasome and the regulation of LXRs signaling is a potential therapeutic for inflammasome-driven diseases.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shui-Xing
authors.initials: SX
authors.lastname: Yu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Xiao-Zhu
authors.initials: XZ
authors.lastname: Hu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Feng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Kun-Yu
authors.initials: KY
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Qi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Lei
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Gui-Qiu
authors.initials: GQ
authors.lastname: Hu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Ma
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Chong-Tao
authors.initials: CT
authors.lastname: Du
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: youngjune@jlu.edu.cn.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000276:immunology; D002460:Cell Line; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D000071518:Liver X Receptors / Q000819:agonists* / Q000276:immunology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071518:Liver X Receptors; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Inflammasome; Inflammation; LXRs agonists; NLRP3; mtROS