title: Genipin suppresses NLRP3 inflammasome activation through uncoupling protein-2.
abstract: Incomplete clearance of apoptotic cells and reactive oxygen species (ROS) release are known to trigger inflammasome activation causing severe inflammation in acute lung injury and various metabolic and autoimmune diseases. Moreover, it has been reported that apoptotic cell clearance and ROS-mediated apoptosis critically depend on mitochondrial uncoupling protein-2 (UCP2). However, the relationship between UCP2 and inflammasome activation has not been studied. This report investigates the role of UCP2 in the expression and activation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in human macrophages. We found that UCP2 overexpression significantly enhanced the expression levels of NLRP3. The NLRP3 expression levels were significantly suppressed in THP1 cells treated with genipin, a UCP2 inhibitor, compared to controls. In addition, genipin altered adenosine triphosphate (ATP)- and hydrogen peroxide (H2O2)-mediated interleukin-1 beta (IL-1β) secretion and significantly suppressed caspase-1 activity in inflammasome-activated human macrophages. Taken together, our results suggest that genipin modulates NLRP3 inflammasome activation and ATP- or H2O2-mediated IL-1β release.
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Rajanbabu
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Galam
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Jutaro
authors.initials: J
authors.lastname: Fukumoto
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Enciso
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Pratima
authors.initials: P
authors.lastname: Tadikonda
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Troy N
authors.initials: TN
authors.lastname: Lane
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Sayantani
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Prasanna Tamarapu
authors.initials: PT
authors.lastname: Parthasarathy
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.affiliation: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. Electronic address: nkollipu@health.usf.edu.
authors.forename: Narasaiah
authors.initials: N
authors.lastname: Kolliputi
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D039823:Iridoids / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000276:immunology; D000071246:Uncoupling Protein 2
chemical_list: D002352:Carrier Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D007473:Ion Channels; D039823:Iridoids; D024101:Mitochondrial Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; C007834:genipin; D020170:Caspase 1
keywords: ASC; Caspase-1; IL-1β; Nigericin; THP1