title: The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome.
abstract: BACKGROUND
  Antrodia cinnamomea--a medicinal fungus that is indigenous to Taiwan--has been used as a health tonic by aboriginal tribes and the Asian population. Recent studies indicate that Antrodia cinnamomea extracts exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory, immuno-modulatory, and anti-cancer effects on cultured cells and laboratory animals. This study aims to explore the anti-inflammatory activity of an Antrodia cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1 macrophages.
  
  
  METHODS
  The effects of ACEE on cell viability were studied using the MTT assay. The expressions of genes, proteins, and pro-inflammatory cytokines were measured by quantitative real-time RT-PCR, Western blotting and ELISA, respectively. The ACEE was further investigated for its effects on reactive oxygen species (ROS) production using ROS detection kit.
  
  
  RESULTS
  Our results showed that ACEE significantly inhibits ATP-induced secretion of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) by LPS-primed macrophages. ACEE also suppresses the transcription and activation of caspase-1, which is responsible for the cleavage and activation of IL-1β and IL-18. Of note, ACEE not only reduces expression of the inflammasome component NLRP3 and the purinergic receptor P2X7R but also inhibits ATP-induced ROS production and caspase-1 activation. Furthermore, the anti-inflammatory properties of ACEE correlate with reduced activation of the MAPK and NF-κB pathways.
  
  
  CONCLUSIONS
  The results of the present study indicate that Antrodia cinnamomea suppresses the secretion of IL-1β and IL-18 associated with inhibition of the NLRP3 inflammasome in macrophages. These findings suggest that ACEE may have therapeutic potential for the treatment of inflammatory diseases.
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Tsung-Teng
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Sian-Pu
authors.initials: SP
authors.lastname: Wu
authors.affiliation: Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Kowit-Yu
authors.initials: KY
authors.lastname: Chong
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Molecular Cell Biology and Health Sciences Research Institute, University of California, Merced, Merced, CA 95343, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei 24301, Taiwan; Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Ko
authors.affiliation: Cancer Research Center, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Cheng-Yeu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Respiratory Therapy, Fu Jen Catholic University, Taipei 24205, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Jan
authors.initials: J
authors.lastname: Martel
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei 24301, Taiwan; Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan; Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA. Electronic address: dingeyoung@hotmail.com.
authors.forename: John D
authors.initials: JD
authors.lastname: Young
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: hclai@mail.cgu.edu.tw.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008518:Medicine, East Asian Traditional / Q000379:methods; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D020170:Caspase 1
keywords: Anti-inflammatory activity; Antrodia cinnamomea; Caspase-1; Inflammasome; NLRP3; Reactive oxygen species