Journal
CYTOKINE
Volume 91, Issue -, Pages 30-37Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2016.12.003
Keywords
Inflammation; Inflammasome; NLRP3; mtROS; LXRs agonists
Funding
- National Natural Science Foundation of China [31172298, 31372410]
- National Key Basic Research Program of China [2011CB944404]
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Inflammasomes are multiprotein complexes that control the production of IL-1 beta 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-1 beta 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 LXR5 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. (C) 2016 Elsevier Ltd. All rights reserved.
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