title: NLRP3 deletion protects from hyperoxia-induced acute lung injury.
abstract: Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3(-/-) mice were exposed to 100% O2 for 48-72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3(-/-) mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNFα, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3(-/-) mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-κB levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.
authors: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
authors: Jutaro
authors: J
authors: Fukumoto
authors: Itsuko
authors: I
authors: Fukumoto
authors: Prasanna Tamarapu
authors: PT
authors: Parthasarathy
authors: Ruan
authors: R
authors: Cox
authors: Bao
authors: B
authors: Huynh
authors: Gurukumar Kollongod
authors: GK
authors: Ramanathan
authors: Rajan Babu
authors: RB
authors: Venugopal
authors: Diane S
authors: DS
authors: Allen-Gipson
authors: Richard F
authors: RF
authors: Lockey
authors: Narasaiah
authors: N
authors: Kolliputi
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism; D058847:Inflammasomes / Q000009:adverse effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen
keywords: hyperoxia; inflammation; injury; lung; reactive oxygen species
references: Am J Physiol Lung Cell Mol Physiol. 2008 Sep;295(3):L379-99
references: 18621912
references: J Appl Physiol Respir Environ Exerc Physiol. 1979 Jul;47(1):98-103
references: 224021
references: Inflammation. 2000 Aug;24(4):289-303
references: 10850852
references: Am J Pathol. 2002 Dec;161(6):2283-94
references: 12466142
references: J Immunol. 1996 Mar 1;156(5):1963-72
references: 8596051
references: FEBS Lett. 1997 Mar 24;405(2):213-8
references: 9089293
references: Am J Pathol. 2004 Jun;164(6):1949-58
references: 15161631
references: Arch Immunol Ther Exp (Warsz). 2004 Nov-Dec;52(6):435-40
references: 15577745
references: Mol Biol Cell. 2002 Sep;13(9):3218-34
references: 12221127
references: Mol Cell. 2002 Aug;10(2):417-26
references: 12191486
references: Clin Exp Immunol. 2011 Oct;166(1):1-15
references: 21762124
references: J Biol Chem. 2011 Mar 25;286(12):10660-70
references: 21247898
references: Am Rev Respir Dis. 1992 Aug;146(2):427-32
references: 1489135
references: Res Rep Health Eff Inst. 1993 Jan;(54):1-30; discussion 31-9
references: 8439407
references: Sci Signal. 2010 Jan 19;3(105):cm1
references: 20086235
references: Am J Respir Crit Care Med. 2008 Oct 15;178(8):805-13
references: 18635887
references: J Clin Invest. 1998 May 1;101(9):1970-82
references: 9576762
references: Respir Care. 2013 Jan;58(1):123-41
references: 23271823
references: J Immunol. 2004 Feb 15;172(4):2668-77
references: 14764742
references: Mol Med. 2011 Mar-Apr;17(3-4):293-307
references: 21046059
references: Respir Res. 2002;3:25
references: 12537603
references: Free Radic Biol Med. 2007 Apr 1;42(7):897-908
references: 17349918
references: Immunology. 1990 Apr;69(4):548-53
references: 2185985
references: Am J Respir Cell Mol Biol. 2000 May;22(5):535-42
references: 10783124
references: Science. 2008 May 2;320(5876):619-20
references: 18451288
references: J Biol Chem. 2008 Sep 19;283(38):25900-12
references: 18515365
references: Am J Physiol. 1997 May;272(5 Pt 1):L852-9
references: 9176248
references: J Clin Invest. 2005 Apr;115(4):1039-48
references: 15841185
references: Respir Res. 2006 Oct 11;7:125
references: 17034639
references: Am J Pathol. 2004 Nov;165(5):1819-26
references: 15509550
references: J Surg Res. 2002 Mar;103(1):61-7
references: 11855919
references: J Immunol. 2011 Nov 1;187(9):4809-17
references: 21940680
references: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1137-45
references: 11076804
references: J Neuroimmunol. 1992 Feb;36(2-3):179-91
references: 1732280
references: J Biol Chem. 1996 Jul 12;271(28):16591-6
references: 8663179
references: Chest. 2011 Sep;140(3):768-774
references: 21896520
references: J Clin Invest. 1981 Nov;68(5):1277-88
references: 7298852
references: Immunity. 2010 May 28;32(5):593-604
references: 20510870
references: Circ Res. 2008 Apr 11;102(7):804-12
references: 18276918
references: J Immunol. 1992 Apr 15;148(8):2423-8
references: 1348518
references: Science. 2010 Oct 15;330(6002):362-6
references: 20947763
references: J Cell Physiol. 2012 Sep;227(9):3310-6
references: 22169929
references: J Immunol. 2010 May 15;184(10):5819-26
references: 20375306
references: Cell. 2006 Aug 25;126(4):659-62
references: 16923387
references: Int J Exp Pathol. 2006 Dec;87(6):475-83
references: 17222215
references: J Clin Invest. 1983 Mar;71(3):754-61
references: 6600748
references: Am J Physiol Lung Cell Mol Physiol. 2000 Jul;279(1):L25-35
references: 10893199
references: J Immunol. 2004 Mar 15;172(6):3860-8
references: 15004193
references: Crit Care Med. 2000 Jul;28(7):2437-44
references: 10921576
references: Science. 2008 May 2;320(5876):674-7
references: 18403674
references: J Immunol. 2009 Jun 1;182(11):7264-71
references: 19454723