Please use this identifier to cite or link to this item: https://doi.org/10.3389/fimmu.2020.607564
Title: A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction
Authors: Wu, C.-H.
Gan, C.H. 
Li, L.-H.
Chang, J.-C.
Chen, S.-T.
Menon, M.P.
Cheng, S.-M.
Yang, S.-P.
Ho, C.-L.
Chernikov, O.V.
Lin, C.-H.
Lam, Y. 
Hua, K.-F.
Keywords: autophagy
conjugated polyenes
mitochondria
NLRP3 inflammasome
peritonitis
Issue Date: 2020
Publisher: Frontiers Media S.A.
Citation: Wu, C.-H., Gan, C.H., Li, L.-H., Chang, J.-C., Chen, S.-T., Menon, M.P., Cheng, S.-M., Yang, S.-P., Ho, C.-L., Chernikov, O.V., Lin, C.-H., Lam, Y., Hua, K.-F. (2020). A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction. Frontiers in Immunology 11 : 607564. ScholarBank@NUS Repository. https://doi.org/10.3389/fimmu.2020.607564
Rights: Attribution 4.0 International
Abstract: Conjugated polyenes are a class of widely occurring natural products with various biological functions. We previously identified 4-hydroxy auxarconjugatin B (4-HAB) as anti?inflammatory agent with an IC50 of ~20 µM. In this study, we synthesized a new anti?inflammatory 4-HAB analogue, F240B, which has an IC50 of less than 1 µM. F240B dose-dependently induced autophagy by increasing autophagic flux, LC3 speck formation and acidic vesicular organelle formation. F240B inhibited NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome activation through autophagy induction. In a mechanistic study, F240B inhibited interleukin (IL)-1? (IL-1?) precursor expression, promoted degradation of NLRP3 and IL-1?, and reduced mitochondrial membrane integrity loss in an autophagy-dependent manner. Additionally, F240B inhibited apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and speck formation without affecting the interaction between NLRP3 and ASC or NIMA-related kinase 7 (NEK7) and double-stranded RNA-dependent kinase (PKR). Furthermore, F240B exerted in vivo anti-inflammatory activity by reducing the intraperitoneal influx of neutrophils and the levels of IL-1?, active caspase-1, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in lavage fluids in a mouse model of uric acid crystal-induced peritonitis. In conclusion, F240B attenuated the NLRP3 inflammasome through autophagy induction and can be developed as an anti-inflammatory agent in the future. © Copyright © 2020 Wu, Gan, Li, Chang, Chen, Menon, Cheng, Yang, Ho, Chernikov, Lin, Lam and Hua.
Source Title: Frontiers in Immunology
URI: https://scholarbank.nus.edu.sg/handle/10635/196270
ISSN: 1664-3224
DOI: 10.3389/fimmu.2020.607564
Rights: Attribution 4.0 International
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