title: Inflammasome Activity in Non-Microbial Lung Inflammation.
abstract: The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer.
authors: Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, USA.
authors: Jennifer L
authors: JL
authors: Ather
authors: Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, USA.
authors: Rebecca A
authors: RA
authors: Martin
authors: Chemistry Department, State University of New York at Plattsburgh, Plattsburgh, USA.
authors: Karina
authors: K
authors: Ckless
authors: Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, USA.
authors: Matthew E
authors: ME
authors: Poynter
keywords: IL-1; IL-18; inflammasome; inflammation; lung
references: J Exp Med. 2006 Jul 10;203(7):1685-91
references: 16818675
references: Immunol Rev. 2011 Sep;243(1):191-205
references: 21884177
references: Int Immunopharmacol. 2012 Dec;14(4):504-12
references: 23044435
references: J Neuroinflammation. 2006 Mar 16;3:5
references: 16542445
references: Am J Respir Cell Mol Biol. 2013 May;48(5):655-64
references: 23371061
references: Am J Respir Crit Care Med. 2009 Oct 15;180(8):720-30
references: 19661246
references: Immunity. 2009 Jun 19;30(6):860-74
references: 19501001
references: J Allergy Clin Immunol. 2009 May;123(5):1185-7
references: 19361847
references: Nature. 2011 Jan 13;469(7329):221-5
references: 21124315
references: J Immunol. 2013 Apr 1;190(7):3590-9
references: 23436933
references: Nat Med. 2013 Jan;19(1):57-64
references: 23202296
references: Hum Exp Toxicol. 2012 Nov;31(11):1113-31
references: 22699116
references: Mediators Inflamm. 2009;2009:958658
references: 19901996
references: Rheumatol Int. 1990;10(5):217-9
references: 2075374
references: Nat Immunol. 2012 Mar 18;13(4):343-51
references: 22430787
references: Am J Respir Crit Care Med. 2012 Jun 1;185(11):1205-17
references: 22383501
references: Toxicol Appl Pharmacol. 1997 Aug;145(2):331-9
references: 9266806
references: Mol Nutr Food Res. 2012 Aug;56(8):1212-22
references: 22700321
references: Sci Total Environ. 2012 May 15;425:110-8
references: 22475217
references: Free Radic Biol Med. 2013 Jul;60:233-45
references: 23376234
references: Clin Immunol. 2010 Nov;137(2):234-41
references: 20797910
references: J Allergy Clin Immunol. 2001 Sep;108(3):430-8
references: 11544464
references: Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19449-54
references: 20974980
references: J Immunol. 2008 Sep 15;181(6):4089-97
references: 18768865
references: J Mol Cell Biol. 2012 Feb;4(1):3-10
references: 22147847
references: J Immunol. 2012 Jun 1;188(11):5623-35
references: 22547706
references: Curr Opin Immunol. 2010 Feb;22(1):28-33
references: 20060699
references: J Allergy Clin Immunol. 2009 Oct;124(4):761-70.e1
references: 19815118
references: Anesthesiology. 2012 May;116(5):1104-15
references: 22531249
references: Eur Respir J. 1996 Oct;9(10):2036-43
references: 8902464
references: Nat Immunol. 2012 Jan 29;13(3):255-63
references: 22286270
references: Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 2):S9-S16
references: 12471083
references: Cancer Res. 2012 Nov 15;72 (22):5721-32
references: 22986739
references: Pulm Pharmacol Ther. 2012 Dec;25(6):438-46
references: 22579987
references: PLoS One. 2011;6(9):e24097
references: 21915284
references: J Biol Eng. 2012 Nov 13;6(1):22
references: 23148460
references: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9035-40
references: 18577586
references: J Immunol. 2012 Mar 15;188(6):2884-93
references: 22323538
references: Immunity. 2011 Apr 22;34(4):527-40
references: 21474346
references: Radiol Clin North Am. 2012 Sep;50(5):863-76
references: 22974775
references: Eur J Immunol. 2011 May;41(5):1203-17
references: 21523780
references: J Allergy Clin Immunol. 2005 May;115(5):897-909; quiz 910
references: 15867841
references: Allergol Int. 2012 Jun;61(2):231-43
references: 22361514
references: J Immunol. 2012 Dec 1;189(11):5113-7
references: 23100513
references: J Immunol. 2011 Sep 15;187(6):3331-7
references: 21844393
references: Nat Med. 2012 Mar 04;18(4):547-54
references: 22388091
references: Pediatr Int. 2012 Dec;54(6):762-9
references: 22640481
references: Nature. 2008 Jun 19;453(7198):1122-6
references: 18496530
references: Immunol Cell Biol. 2012 Nov;90(10 ):983-6
references: 23010873
references: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3030-3
references: 20133696
references: Nature. 2006 Mar 9;440(7081):237-41
references: 16407889
references: J Leukoc Biol. 2011 Mar;89(3):383-92
references: 20952658
references: Med Clin North Am. 2012 Jul;96(4):713-27
references: 22793940
references: Nat Immunol. 2013 Jan;14 (1):52-60
references: 23160153
references: Immunol Res. 2012 Jun;52(3):182-99
references: 22160809
references: J Biol Chem. 1999 Nov 26;274(48):33835-8
references: 10567338
references: Biochim Biophys Acta. 2011 Nov;1810(11):1025-34
references: 21397661
references: J Neurosci. 2010 Nov 24;30(47):15811-20
references: 21106820
references: Nat Med. 2011 Feb;17 (2):179-88
references: 21217695
references: Nat Immunol. 2008 Aug;9(8):847-56
references: 18604214
references: Nat Immunol. 2010 Feb;11(2):136-40
references: 20023662
references: PLoS One. 2012;7(1):e30612
references: 22291998
references: Int Immunol. 2003 Apr;15(4):483-90
references: 12663678
references: Crit Rev Toxicol. 2009;39(9):743-81
references: 19852560
references: Am J Respir Crit Care Med. 2007 Oct 1;176(7):650-8
references: 17641156
references: Nat Genet. 2006 Feb;38(2):240-4
references: 16429160
references: J Allergy Clin Immunol. 2013 Jun;131(6):1528-36
references: 23403049
references: US Neurol. 2010;6(2):19-27
references: 22408651
references: J Exp Med. 2012 Jul 30;209(8):1505-17
references: 22802353
references: Science. 2008 May 2;320(5876):674-7
references: 18403674
references: J Leukoc Biol. 2013 Apr;93(4):489-97
references: 23271701
references: Int Immunopharmacol. 2006 Oct;6(10):1569-76
references: 16919829
references: Blood. 1996 Mar 15;87(6):2095-147
references: 8630372
references: Thorax. 2013 Jan;68(1):82-90
references: 23093652
references: Chest. 2000 Nov;118(5):1315-21
references: 11083680
references: Nat Immunol. 2012 Mar 19;13(4):333-42
references: 22430786
references: Eur J Immunol. 2010 Mar;40(3):616-9
references: 20201014
references: Free Radic Biol Med. 2012 Aug 15;53(4):721-9
references: 22683820
references: Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1061-6
references: 8887608
references: Front Immunol. 2012 Oct 09;3:315
references: 23087690
references: Proc Am Thorac Soc. 2009 May 1;6(3):249-55
references: 19387025
references: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20388-93
references: 19918053
references: Am J Respir Cell Mol Biol. 2011 May;44(5):631-8
references: 20581095
references: Am J Physiol Cell Physiol. 2004 Oct;287(4):C817-33
references: 15355853
references: PLoS One. 2008 Apr 30;3(4):e2119
references: 18446235
references: Part Fibre Toxicol. 2012 Aug 06;9:31
references: 22867088
references: J Immunol. 2011 Nov 1;187(9):4809-17
references: 21940680
references: Nat Rev Immunol. 2010 Mar;10 (3):210-5
references: 20168318
references: Am J Physiol Lung Cell Mol Physiol. 2006 Jan;290(1):L144-52
references: 16085673
references: Cell Metab. 2012 Jan 4;15(1):10-8
references: 22225872
references: J Leukoc Biol. 2012 Nov;92 (5):951-8
references: 22859832
references: Nat Immunol. 2012 Mar 19;13(4):325-32
references: 22430785
references: J Immunol. 2007 Feb 1;178(3):1948-59
references: 17237446
references: J Biol Chem. 2005 Apr 15;280(15):15122-30
references: 15701651
references: Arch Intern Med. 1999 Nov 22;159(21):2582-8
references: 10573048
references: Oncogene. 2001 Oct 1;20(44):6473-81
references: 11607846
references: J Immunol. 2011 Jul 1;187(1):64-73
references: 21622869
references: J Allergy Clin Immunol. 2009 Oct;124(4):779-85.e6
references: 19767079
references: Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L732-9
references: 11504702
references: Arthritis Rheum. 2004 Feb;50(2):607-12
references: 14872505
references: J Biol Chem. 2011 Jun 17;286(24):21844-52
references: 21525001
references: Blood. 2010 Jan 21;115(3):530-40
references: 19965648
references: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L856-65
references: 16373670
references: Nanotoxicology. 2013 Dec;7(8):1302-14
references: 23020093
references: Biochem Biophys Res Commun. 2001 Jun 1;284(1):77-82
references: 11374873
references: Eur Respir J. 2011 Nov;38(5):1019-28
references: 21622588
references: J Immunol. 2008 Sep 15;181(6):3755-9
references: 18768827
references: J Immunol. 2011 May 15;186(10 ):5738-48
references: 21471445
references: J Immunol. 1997 Oct 1;159(7):3364-71
references: 9317135
references: Eur J Immunol. 2008 Aug;38(8):2085-9
references: 18624356
references: Am J Physiol Lung Cell Mol Physiol. 2013 Mar 1;304(5):L312-23
references: 23292810
references: Respir Res. 2011 Jun 23;12:86
references: 21699702
references: Toxicol Sci. 2008 Sep;105(1):188-99
references: 18515264
references: Mol Cell Biochem. 2002 May-Jun;234-235(1-2):71-80
references: 12162462
references: Endocrinology. 2011 Nov;152(11):4039-45
references: 21862613
references: J Exp Med. 2012 Feb 13;209(2):251-8
references: 22291094
references: Curr Opin Lipidol. 2012 Dec;23(6):548-53
references: 23069985
references: Toxicol Sci. 2011 Nov;124(1):138-48
references: 21828359
references: Eur J Immunol. 2011 Jul;41(7):2040-51
references: 21484785
references: Ann Med. 2007;39(8):581-93
references: 18038361
references: J Allergy Clin Immunol. 2011 Mar;127(3):806-14.e1-4
references: 21272927
references: Inhal Toxicol. 2012 Dec;24(14 ):995-1008
references: 23216160
references: Immunity. 2004 Mar;20(3):319-25
references: 15030775
references: J Exp Med. 2010 Mar 15;207(3):535-52
references: 20176803
references: J Allergy Clin Immunol. 2010 May;125(5):1028-1036.e13
references: 20398920
references: Ann Intensive Care. 2012 Jul 12;2(1):27
references: 22788849
references: Biochim Biophys Acta. 2011 Nov;1810(11):1120-6
references: 21944975
references: Inhal Toxicol. 2009 Aug;21(10):812-8
references: 19225964
references: J Allergy Clin Immunol. 1992 May;89(5):958-67
references: 1374772
references: Am J Respir Crit Care Med. 2012 Sep 1;186(5):395-6
references: 22942341
references: Vaccine. 2009 May 18;27(23 ):3013-21
references: 19428913
references: Nat Immunol. 2011 May;12 (5):408-15
references: 21478880
references: Immunol Rev. 2012 Sep;249(1):239-52
references: 22889226
references: J Immunol. 2007 Sep 15;179(6):3680-8
references: 17785804
references: Chest. 2012 Nov;142(5):1289-99
references: 23131937
references: J Immunol. 2011 Jul 15;187(2):613-7
references: 21677136
references: Pharmacol Ther. 2011 Jun;130(3):364-70
references: 21421008
references: J Immunol. 2008 Jan 15;180(2):1169-78
references: 18178857
references: Nat Immunol. 2010 Oct;11(10 ):897-904
references: 20835230
references: J Immunol. 2011 Nov 15;187(10):5328-35
references: 22003203
references: Nat Rev Drug Discov. 2012 Aug;11(8):633-52
references: 22850787
references: Immunity. 2009 Apr 17;30(4):576-87
references: 19362022
references: J Exp Med. 2008 Apr 14;205(4):869-82
references: 18362170
references: Mol Cell. 2002 Aug;10(2):417-26
references: 12191486
references: Eur J Immunol. 2003 Apr;33(4):991-1000
references: 12672065
references: Lancet. 2012 May 26;379(9830):2008-18
references: 22534002
references: Eur Ann Allergy Clin Immunol. 2011 Oct;43(5):141-56
references: 22145250
references: Am J Respir Crit Care Med. 1999 Feb;159(2):487-94
references: 9927362
references: Respir Res. 2010 Jul 26;11:102
references: 20659336
references: J Immunol. 2012 Oct 15;189(8):4144-53
references: 22972933
references: Biol Pharm Bull. 2012;35(12):2133-40
references: 23207765
references: Nanotoxicology. 2010 Jun;4(2):161-76
references: 20795893
references: Allergy. 2011 Aug;66(8):1047-57
references: 21443539
references: Am J Respir Cell Mol Biol. 2011 Feb;44(2):155-65
references: 20348206
references: Blood. 2010 Sep 2;116(9):1570-3
references: 20495074
references: Endocrinology. 2012 Dec;153(12):5866-74
references: 23117929
references: J Allergy Clin Immunol. 2012 Apr;129(4):1116-25.e6
references: 22227418
references: Environ Health Perspect. 2012 Dec;120(12 ):1692-8
references: 23010656
references: J Immunol. 1994 Jul 15;153(2):712-23
references: 8021507
references: Small. 2013 May 27;9(9-10):1595-607
references: 23180683
references: Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):88-98
references: 16487041
references: Int Arch Allergy Immunol. 2010;151(4):297-307
references: 19844129
references: J Biol Chem. 2007 Feb 2;282(5):2871-9
references: 17132626
references: Nano Lett. 2006 Jun;6(6):1121-5
references: 16771565
references: J Biol Chem. 2009 May 8;284(19):12762-71
references: 19258328
references: Infect Agent Cancer. 2012 Oct 02;7(1):25
references: 23031505
references: Trends Mol Med. 2010 Jul;16(7):321-8
references: 20605742
references: J Immunol. 2010 Jul 15;185(2):974-81
references: 20574004
references: Auton Autacoid Pharmacol. 2011 Jul-Oct;31(3-4):37-49
references: 21951583
references: Respirology. 2013 Apr;18(3):447-54
references: 23145908
references: J Immunol. 2008 Aug 1;181(3):1627-31
references: 18641298
references: Arthritis Rheum. 2009 Dec;60(12):3642-50
references: 19950258
references: PLoS One. 2012;7(1):e29695
references: 22295065
references: Thorax. 2002 Aug;57(8):687-93
references: 12149528
references: J Allergy Clin Immunol. 2002 Feb;109(2):271-3
references: 11842296
references: Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L1023-9
references: 17189320
references: PLoS One. 2011;6(8):e23185
references: 21858022
references: Respir Physiol Neurobiol. 2013 Jan 15;185(2):454-60
references: 22947217
references: Ann N Y Acad Sci. 2012 Jul;1259:39-46
references: 22758635
references: Trends Immunol. 2011 Sep;32(9):402-11
references: 21783420
references: Am J Respir Crit Care Med. 2012 Jun 1;185(11):1225-34
references: 22461369
references: Open Rheumatol J. 2012;6:80-6
references: 22802905