The nuclear factor NF-kappaB pathway in inflammation.
The nuclear factor NF-kappaB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-kappaB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-kappaB has long been considered the "holy grail" as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-kappaB in inflammation in light of these recent studies.
Lawrence
Toby
T
Inflammation Biology Group, Centre d'Immunologie Marseille-Luminy, Parc Scientifique de Luminy, Case 906, 13288 Marseille, France. lawrence@ciml.univ-mrs.fr
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D016328:NF-kappa B
J Immunol. 2004 Jan 15;172(2):752-6
14707043
Nature. 2007 Mar 29;446(7135):557-61
17361131
Science. 2001 Aug 24;293(5534):1495-9
11520989
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15058-63
18815378
Cell. 2001 Dec 14;107(6):763-75
11747812
Cell. 2007 Sep 7;130(5):918-31
17803913
Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11643-8
17606919
Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17723-8
16317067
J Immunol. 2003 Aug 1;171(3):1484-92
12874241
J Exp Med. 2001 Mar 5;193(5):631-6
11238593
Science. 1996 Nov 1;274(5288):782-4
8864118
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5634-9
15064395
Nat Med. 2001 Dec;7(12):1291-7
11726968
Infect Immun. 1999 Apr;67(4):1553-9
10084986
J Exp Med. 1984 Jan 1;159(1):1-20
6693832
Cancer Res. 2006 Dec 1;66(23):11432-40
17145890
J Exp Med. 1998 Jan 19;187(2):147-59
9432973
Immunity. 2002 Oct;17(4):525-35
12387745
Nature. 1995 Feb 2;373(6513):444-8
7530337
J Immunol. 2001 Aug 15;167(4):1909-19
11489970
Mol Cell. 2003 Jun;11(6):1563-74
12820969
J Clin Invest. 1998 Nov 1;102(9):1645-52
9802878
Science. 1999 Apr 9;284(5412):321-5
10195897
Curr Drug Targets. 2006 Jun;7(6):675-81
16787167
J Immunol. 2001 Feb 15;166(4):2705-11
11160335
Trends Immunol. 2004 Jun;25(6):280-8
15145317
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13859-64
9811891
J Immunol. 2001 Feb 1;166(3):1443-7
11160181
J Immunol. 2003 Jun 15;170(12):6257-65
12794158
Cell. 2006 Feb 24;124(4):823-35
16497591
Immunity. 2005 Sep;23(3):319-29
16169504
J Immunol. 2006 Nov 15;177(10):7332-9
17082652
Mol Cell Biol. 1999 Nov;19(11):7688-96
10523657
J Biol Chem. 1999 Jan 8;274(2):987-92
9873041
Am J Pathol. 2002 Apr;160(4):1325-34
11943717
J Exp Med. 1998 Jan 19;187(2):185-96
9432976
Nat Rev Immunol. 2003 Jan;3(1):23-35
12511873
Cell Death Differ. 1999 Jun;6(6):570-82
10381655
Curr Opin Pharmacol. 2007 Aug;7(4):412-7
17627887
Immunity. 2005 Apr;22(4):439-50
15845449
J Exp Med. 2008 Jun 9;205(6):1269-76
18490491
Eur J Immunol. 1999 Mar;29(3):745-54
10092076
J Immunol. 2004 Nov 1;173(9):5786-93
15494531
J Immunol. 1999 Jul 1;163(1):427-33
10384145
Nat Rev Drug Discov. 2004 Jan;3(1):17-26
14708018
Science. 1992 Jun 5;256(5062):1452-6
1604322
Curr Biol. 2005 Jul 26;15(14):1291-5
16051172
J Immunol. 2006 Sep 15;177(6):4080-5
16951372
Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12425-30
16116086
J Immunol. 2004 Dec 1;173(11):7003-9
15557197
Nature. 2008 Jul 24;454(7203):436-44
18650914
Cell. 2006 Feb 24;124(4):783-801
16497588
Am J Pathol. 1997 Aug;151(2):375-87
9250151
J Exp Med. 1995 Nov 1;182(5):1545-56
7595224
J Exp Med. 1999 Jan 4;189(1):145-58
9874571
Cytokine. 2004 Nov 21-Dec 7;28(4-5):152-7
15588688
Cell. 1995 Jan 27;80(2):331-40
7834753
Cell. 2002 Apr;109 Suppl:S81-96
11983155
Nature. 1995 Feb 9;373(6514):531-6
7845467
Immunity. 2006 Sep;25(3):403-15
16973390
J Immunol. 1997 Mar 15;158(6):2558-66
9058787
J Exp Med. 2003 Sep 1;198(5):771-81
12939342
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10626-31
9724754
Int J Exp Pathol. 2007 Apr;88(2):85-94
17408451
J Exp Med. 2001 Feb 19;193(4):417-26
11181694
Cell. 1997 Oct 17;91(2):243-52
9346241
Annu Rev Immunol. 2000;18:621-63
10837071
J Immunol. 2001 Aug 1;167(3):1592-600
11466381
Nat Med. 2003 May;9(5):575-81
12692538
Science. 1998 Sep 11;281(5383):1680-3
9733516
Nat Rev Immunol. 2005 Dec;5(12):953-64
16322748
Methods. 1998 Apr;14(4):381-92
9608509
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14635-40
16192349
Nature. 2005 Apr 28;434(7037):1138-43
15858576
J Clin Invest. 2001 Jan;107(1):7-11
11134171
J Exp Med. 2008 Jun 9;205(6):1261-8
18490490
Immunity. 1998 Dec;9(6):839-47
9881974
Immunity. 2001 Mar;14(3):217-30
11290332
EMBO J. 2004 Oct 27;23(21):4202-10
15470505
Cell. 2007 Jun 1;129(5):903-14
17540171
Biochem Soc Trans. 2007 Apr;35(Pt 2):270-2
17371257