title: Noncanonical Nuclear Factor Kappa B (NF-κB) Signaling and Potential for Therapeutics in Sepsis.
abstract: NF-κB signaling plays a central role in the pathophysiology of severe sepsis and septic shock. Despite tremendous and missed efforts, novel therapeutics for severe sepsis and septic shock are still needed. Many drugs have been designed to target the canonical NF-κB signaling pathway with limited success, potentially due to the nonspecificity of the drugs for other kinases and the interaction of canonical signaling with other pathways. Here, we review the canonical and noncanonical signaling pathways of NF-κB, the cross talk and negative regulation of the two pathways, and the potential for therapeutics arising from the noncanonical NF-κB pathway in relation to the pathophysiology of septic shock.
authors: University of British Columbia, Heart Lung Innovation Research Centre, Critical Care Research Laboratories, St. Paul's Hospital, #166-1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada, Simone.thair@hli.ubc.ca.
authors: Simone
authors: S
authors: Thair
authors: James A
authors: JA
authors: Russell
references: Trends Immunol. 2004 Jun;25(6):280-8
references: 15145317
references: J Biol Chem. 2001 Sep 28;276(39):36530-4
references: 11479302
references: Crit Care Med. 2003 Oct;31(10):2462-9
references: 14530752
references: Crit Care. 2011;15(1):108
references: 21349138
references: Cancer Cell. 2007 Aug;12(2):115-30
references: 17692804
references: Clin Immunol. 2008 Apr;127(1):89-97
references: 18294918
references: J Biol Chem. 2003 Jun 20;278(25):23094-100
references: 12686541
references: Am J Respir Crit Care Med. 2013 Jun 15;187(12):1287-93
references: 23590272
references: Cell. 1998 Dec 11;95(6):759-70
references: 9865694
references: Trends Mol Med. 2007 Nov;13(11):460-9
references: 18029230
references: Nat Med. 2001 Dec;7(12):1291-7
references: 11726968
references: Cell. 1997 Jan 24;88(2):213-22
references: 9008162
references: Nature. 1987 Dec 17-23;330(6149):662-4
references: 3317066
references: Cell. 1996 Jan 26;84(2):299-308
references: 8565075
references: Biochem Pharmacol. 2000 Oct 15;60(8):1143-51
references: 11007952
references: Cancer Cell. 2007 Aug;12(2):131-44
references: 17692805
references: N Engl J Med. 2008 Jan 10;358(2):111-24
references: 18184957
references: Arthritis Rheum. 2000 Apr;43(4):791-800
references: 10765923
references: J Biol Chem. 1985 Feb 25;260(4):2334-44
references: 3882692
references: Crit Care Med. 2005 Nov;33(11):2457-64
references: 16276166
references: Nat Rev Immunol. 2007 Oct;7(10):817-23
references: 17767193
references: J Biol Chem. 2010 Apr 23;285(17):12971-8
references: 20185819
references: Nature. 1998 Sep 17;395(6699):292-6
references: 9751059
references: Crit Care Med. 2001 Jul;29(7):1303-10
references: 11445675
references: Nat Rev Immunol. 2006 Aug;6(8):613-8
references: 16868552
references: Intensive Care Med. 2009 Apr;35(4):678-86
references: 18946659
references: Crit Care Med. 2003 Jul;31(7):2068-71
references: 12847405
references: Nature. 1985 Dec 19-1986 Jan 1;318(6047):665-7
references: 3001529
references: Blood. 2009 Jun 25;113(26):6603-10
references: 19411637
references: Crit Care Med. 2003 Apr;31(4):1250-6
references: 12682500
references: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3792-7
references: 9520446
references: Arch Intern Med. 2005 Jan 10;165(1):75-82
references: 15642878
references: Crit Care Med. 1995 Jul;23(7):1294-303
references: 7600840
references: Arch Intern Med. 1997 Feb 24;157(4):389-93
references: 9046890
references: Crit Care Med. 2002 Jul;30(7):1488-94
references: 12130967
references: J Biol Chem. 1990 Feb 15;265(5):2973-8
references: 2406243
references: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15059-64
references: 14608036
references: Science. 2001 Aug 24;293(5534):1495-9
references: 11520989
references: Immunity. 1997 Nov;7(5):715-25
references: 9390694
references: Nat Immunol. 2010 May;11(5):373-84
references: 20404851
references: N Engl J Med. 2005 Oct 20;353(16):1711-23
references: 16236742
references: Crit Care Med. 2011 Jul;39(7):1641-8
references: 21423001
references: J Biol Chem. 2005 Dec 30;280(52):43056-63
references: 16260783
references: Curr Pharm Des. 2012;18(35):5735-45
references: 22726116
references: Genes Dev. 1999 May 15;13(10):1322-8
references: 10346820
references: Nature. 1997 Feb 6;385(6616):540-4
references: 9020361
references: J Clin Invest. 2011 Dec;121(12):4775-86
references: 22045568
references: Chest. 2005 Sep;128(3):1690-8
references: 16162776
references: Nature. 1997 Aug 7;388(6642):548-54
references: 9252186
references: Mol Cell. 2001 Feb;7(2):401-9
references: 11239468
references: Nat Med. 2007 May;13(5):579-86
references: 17417651
references: Cytokine Growth Factor Rev. 2004 Oct;15(5):353-66
references: 15450251
references: Nat Rev Immunol. 2003 Sep;3(9):745-56
references: 12949498
references: Mol Cell Biol. 2000 Feb;20(4):1170-8
references: 10648602
references: Am J Respir Crit Care Med. 2010 Jan 15;181(2):143-9
references: 19850944
references: Crit Care Med. 1996 Jul;24(7):1125-8
references: 8674323
references: J Immunol. 2011 Feb 15;186(4):2321-8
references: 21257964
references: Arthritis Rheum. 2007 Jul;56(7):2255-66
references: 17599748
references: J Biol Chem. 1984 Jan 10;259(1):686-91
references: 6608523
references: J Biol Chem. 2000 Jul 14;275(28):21081-5
references: 10887201
references: J Biol Chem. 2004 Jul 16;279(29):30099-105
references: 15140882
references: Thorax. 2000 Jul;55(7):603-13
references: 10856322
references: J Biol Chem. 2004 Jun 18;279(25):26243-50
references: 15084608
references: JAMA. 2002 Aug 21;288(7):862-71
references: 12186604
references: Cell. 1998 Dec 11;95(6):749-58
references: 9865693
references: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9803-8
references: 10449775
references: Curr Infect Dis Rep. 2012 Oct;14(5):474-83
references: 22851006
references: Am J Respir Crit Care Med. 2009 Oct 1;180(7):640-8
references: 19590022
references: Science. 1986 Oct 24;234(4775):470-4
references: 3764421
references: Am J Respir Crit Care Med. 2003 Feb 15;167(4):512-20
references: 12426230
references: J Allergy Clin Immunol. 2004 Dec;114(6):1425-33
references: 15577848
references: J Biol Chem. 1985 Feb 25;260(4):2345-54
references: 3871770
references: Hum Genet. 2008 Jul;123(6):661-3
references: 18496716
references: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3503-8
references: 18292232
references: Annu Rev Immunol. 2000;18:621-63
references: 10837071
references: J Innate Immun. 2009;1(2):164-74
references: 19809574
references: N Engl J Med. 1984 Nov 1;311(18):1137-43
references: 6384785
references: Nat Rev Immunol. 2005 Jun;5(6):446-58
references: 15928677
references: N Engl J Med. 2006 Feb 9;354(6):610-21
references: 16467548
references: Immunity. 2004 Oct;21(4):477-89
references: 15485626
references: Shock. 1999 Jul;12(1):17-24
references: 10468047
references: Nat Rev Immunol. 2008 Jul;8(7):533-44
references: 18551128
references: J Leukoc Biol. 2008 Mar;83(3):523-35
references: 17913974
references: Crit Care Med. 1995 Aug;23(8):1430-9
references: 7634816
references: PLoS One. 2012;7(8):e41644
references: 22952582
references: J Biol Chem. 2005 Dec 9;280(49):40578-82
references: 16223731
references: Circulation. 2003 Aug 12;108(6):664-7
references: 12900338
references: Am J Respir Crit Care Med. 2008 Oct 1;178(7):710-20
references: 18635889
references: Science. 2001 Mar 16;291(5511):2162-5
references: 11251123
references: Crit Care Med. 1998 Apr;26(4):645-50
references: 9559600
references: Nat Med. 1997 Jun;3(6):678-81
references: 9176497