Induction of Cytokines and Chemokines by Toll-like Receptor Signaling: Strategies for Control of Infammation

Critical Reviews in Immunology

Volumn 30, Issue 1, 2010, Pages 53-67

  Zeytun, Ahmet ^a   Chaudhary, Anu ^a   Pardington, Paige ^a   Cary, R Bruce ^b   Gupta, Goutam ^a  

^a LOS ALAMOS NATIONAL LABORATORY   (United States)

^b Mesa Tech International   (United States)

Author keywords

Chemokines; Control mechanisms; Cytokines; Inflammation; TLR pathways

Indexed keywords

CHEMOKINE; CYTOKINE; TOLL LIKE RECEPTOR;

AUTOIMMUNE DISEASE; CONTROLLED STUDY; CYTOKINE PRODUCTION; HOST RESISTANCE; HUMAN; INFLAMMATION; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TISSUE INJURY; ANIMAL; IMMUNOLOGY;

ANIMALS; CYTOKINES; HUMANS; INFLAMMATION; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 77951019151     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevimmunol.v30.i1.40     Document Type: Review

References (117)

1. Akashi S, Saitoh S, Wakabayashi Y, Kikuchi T, Takamura N, Nagai Y, Kusumoto Y, Fukase K, Kusumoto S, Adachi Y, Kosugi A, Miyake K. Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14. J Exp Med. 2003 Oct 6;198(7):1035-1042.
2. Barton GM, Medzhitov R. Toll-like receptors and their ligands. Curr Top Microbiol Immunol. 2002;270: 81-92.
3. Beutler B, Hoebe K, Du X, Ulevitch RJ. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J Leukoc Biol. 2003 Oct;74(4):479-485.
4. Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun. 2009 Oct 30;388(4):621-625.
5. Netea MG, van der Graaf C, Van der Meer JW, Kullberg BJ. Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system. J Leukoc Biol. 2004 May;75(5):749-755.
6. Tanji T, Ip Y T. Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol. 2005 Apr;26(4):193-198.
7. Bowie A, ONeill LA. Te interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-infammatory interleukins and microbial products. J Leukoc Biol. 2000 Apr;67(4):508-514.
8. Dalpke A, Heeg K. Signal integration following Toll-like receptor triggering. Crit Rev Immunol. 2002;22(3):217-250.
9. Daun JM, Fenton MJ. Interleukin-1/Toll receptor family members: receptor structure and signal trans-duction pathways. J Interferon Cytokine Res. 2000 Oct;20(10):843-855.
10. Lee MS, Kim YJ. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem. 2007;76:447-480.
11. Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta. 2002 Nov 11;1592(3):265-280.
12. ONeill LA. Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily. Curr Top Microbiol Immunol. 2002;270:47-61.
13. Ruse M, Knaus UG. New players in TLR-mediated innate immunity: PI3K and small Rho GTPases. Immunol Res. 2006;34(1):33-48.
14. Zeytun A, van Velkinburgh JC, Pardington PE, Cary RR, Gupta G. Pathogen-specifc innate immune response. Adv Exp Med Biol. 2007;598:342-357.
15. Beutler B. Endotoxin, toll-like receptor 4, and the aferent limb of innate immunity. Curr Opin Microbiol. 2000 Feb;3(1):23-28.
16. Beutler B. TLR4 as the mammalian endotoxin sensor. Curr Top Microbiol Immunol. 2002;270:109-120.
17. Dziarski R, Gupta D. Role of MD-2 in TLR2-and TLR4-mediated recognition of Gram-negative and Gram-positive bacteria and activation of chemokine genes. J Endotoxin Res. 2000;6(5):401-405.
18. Dziarski R, Gupta D. Peptidoglycan recognition in innate immunity. J Endotoxin Res. 2005;11(5): 304-310.
19. Edwards MR, Slater L, Johnston SL. Signalling pathways mediating type I interferon gene expression. Microbes Infect. 2007 Sep;9(11):1245-1251.
20. Akira S, Takeda K. Functions of toll-like receptors: lessons from KO mice. C R Biol. 2004 Jun;327(6): 581-589.
21. ONeill LA, Bowie AG. Te family of fve: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007 May;7(5):353-364.
22. Sheedy FJ, ONeill LA. Te Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. J Leukoc Biol. 2007 Aug;82(2):196-203.
23. Yamamoto M, Takeda K, Akira S. TIR domain-containing adaptors defne the specifcity of TLR signaling. Mol Immunol. 2004 Feb;40(12):861-868.
24. Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE. 2006 Oct 17;2006(357):re13.
25. Hessle CC, Andersson B, Wold AE. Gram-positive and Gram-negative bacteria elicit diferent patterns of pro-infammatory cytokines in human monocytes. Cytokine. 2005 Jun 21;30(6):311-318.
26. Hirata N, Yanagawa Y, Ebihara T, Seya T, Uematsu S, Akira S, Hayashi F, Iwabuchi K, Onoé K. Selective synergy in anti-infammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells. Mol Immunol. 2008 May;45(10):2734-2742.
27. Kawai T, Akira S. Signaling to NF-kappaB by Tolllike receptors. Trends Mol Med. 2007 Nov;13(11): 460-469.
28. Gay NJ, Ganglof M. Structure and function of Toll receptors and their ligands. Annu Rev Biochem. 2007;76:141-165.
29. Jin MS, Lee JO. Structures of the toll-like receptor family and its ligand complexes. Immunity. 2008 Aug 15;29(2):182-191.
30. Jerala R. Structural biology of the LPS recognition. Int J Med Microbiol. 2007 Sep;297(5):353-363.
31. Meng J, Parroche P, Golenbock DT, McKnight CJ. Te diferential impact of disulfde bonds and N-linked glycosylation on the stability and function of CD14. J Biol Chem. 2008 Feb 8;283(6):3376-3384.
32. Taylor AH, Heavner G, Nedelman M, Sherris D, Brunt E, Knight D, Ghrayeb J. Lipopolysaccharide (LPS) neutralizing peptides reveal a lipid A binding site of LPS binding protein. J Biol Chem. 1995 Jul 28;270(30):17934-17938.
33. Ganglof M, Gay NJ. MD-2: the Toll 'gatekeeper in endotoxin signalling. Trends Biochem Sci. 2004 Jun;29(6):294-300.
34. Miyake K. Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol. 2004 Apr;12(4):186-192. (Pubitemid 38393739)
35. Visintin A, Iliev DB, Monks BG, Halmen KA, Golenbock DT. Md-2. Immunobiology. 2006;211(6-8):437-447.
36. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. Te structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009 Apr 30;458(7242):1191-1195.
37. Resman N, Vasl J, Oblak A, Pristovsek P, Gioannini TL, Weiss J P, Jerala R. Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J Biol Chem. 2009 May 29;284(22):15052-15060.
38. Saitoh S, Akashi S, Yamada T, Tanimura N, Matsumoto F, Fukase K, Kusumoto S, Kosugi A, Miyake K. Ligand-dependent Toll-like receptor 4 (TLR4)-oligomerization is directly linked with TLR4-signaling. J Endotoxin Res. 2004;10(4):257-260.
39. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol. 1999 Jul 1;163(1):1-5.
40. Zahringer U, Lindner B, Inamura S, Heine H, Alexander C. TLR2-promiscuous or specifc? A critical re-evaluation of a receptor expressing apparent broad specifcity. Immunobiology. 2008;213(3-4): 205-224.
41. Motoyama K, Arima H, Nishimoto Y, Miyake K, Hirayama F, Uekama K. Involvement of CD14 in the inhibitory efects of dimethyl-alpha-cyclodextrin on lipopolysaccharide signaling in macrophages. FEBS Lett. 2005 Mar 14;579(7):1707-1714.
42. Fort MM, Mozafarian A, Stöver AG, Correia Jda S, Johnson DA, Crane RT, Ulevitch RJ, Persing DH, Bielefeldt-Ohmann H, Probst P, Jefery E, Fling SP, Hershberg RM. A synthetic TLR4 antagonist has anti-infammatory efects in two murine models of infammatory bowel disease. J Immunol. 2005 May 15;174(10):6416-6423.
43. Ianaro A, Tersigni M, DAcquisto F. New insight in LPS antagonist. Mini Rev Med Chem. 2009 Mar;9(3):306-317.
44. Leon CG, Tory R, Jia J, Sivak O, Wasan KM. Discovery and development of toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases. Pharm Res. 2008 Aug;25(8):1751-1761.
45. Visintin A, Halmen KA, Latz E, Monks BG, Golenbock DT. Pharmacological inhibition of endotoxin responses is achieved by targeting the TLR4 coreceptor, MD-2. J Immunol. 2005 Nov 15;175(10):6465-6472.
46. Chang YC, Kao WC, Wang WY, Wang WY, Yang RB, Peck K. Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses. Faseb J. 2009 Sep;23(9):3078-3088.
47. Spyvee MR, Zhang H, Hawkins LD, Chow JC. Tolllike receptor 2 antagonists. Part 1: preliminary SAR investigation of novel synthetic phospholipids. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5494-5498.
48. Kuroishi T, Tanaka Y, Sakai A, Sugawara Y, Komine K, Sugawara S. Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells. Mol Immunol. 2007 Mar; 44(8):1969-1976.
49. LeBouder E, Rey-Nores JE, Rushmere NK, Grigorov M, Lawn SD, Afolter M, Grifn GE, Ferrara P, Schifrin EJ, Morgan BP, Labéta MO. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol. 2003 Dec 15;171(12):6680-6689.
50. Cavaillon JM, Adib-Conquy M. Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis. Crit Care. 2006;10(5):233.
51. Kariko K, Weissman D, Welsh FA. Inhibition of toll-like receptor and cytokine signaling-a unifying theme in ischemic tolerance. J Cereb Blood Flow Metab. 2004 Nov;24(11):1288-1304.
52. Kawana H, Karaki H, Higashi M, Miyazaki M, Hilberg F, Kitagawa M, Harigaya K. CD44 suppresses TLR-mediated infammation. J Immunol. 2008 Mar 15;180(6):4235-4245.
53. Liang J, Jiang D, Grifth J, Yu S, Fan J, Zhao X, Bucala R, Noble PW. CD44 is a negative regulator of acute pulmonary infammation and lipopolysaccharide- TLR signaling in mouse macrophages. J Immunol. 2007 Feb 15;178(4):2469-2475.
54. Henning LN, Azad AK, Parsa KV, Crowther JE, Tridandapani S, Schlesinger LS. Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages. J Immunol. 2008 Jun 15;180(12):7847-7858.
55. Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Torac Soc. 2007 Jul;4(3):252-257.
56. Park CT, Creasey AA, Wright SD. Tissue factor pathway inhibitor blocks cellular efects of endotoxin by binding to endotoxin and interfering with transfer to CD14. Blood. 1997 Jun 15;89(12):4268-4274.
57. Janssens S, Beyaert R. A universal role for MyD88 in TLR/IL-1R-mediated signaling. Trends Biochem Sci. 2002 Sep;27(9):474-482.
58. Kawai T, Takeuchi O, Fujita T, Inoue J, Mühlradt PF, Sato S, Hoshino K, Akira S. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001 Nov 15;167(10):5887-5894.
59. Laird MH, Rhee SH, Perkins DJ, Medvedev AE, Piao W, Fenton MJ, Vogel SN. TLR4/MyD88/PI3K interactions regulate TLR4 signaling. J Leukoc Biol. 2009 Jun;85(6):966-977.
60. Wang Q, Dziarski R, Kirschning CJ, Muzio M, Gupta D. Micrococci and peptidoglycan activate TLR2->MyD88->IRAK->TRAF->NIK->IKK->NF- kappaB signal transduction pathway that induces transcription of interleukin-8. Infect Immun. 2001 Apr;69(4):2270-2276.
61. Verstak B, Nagpal K, Bottomley SP, Golenbock DT, Hertzog PJ, Mansell A. MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2-and TLR4-mediated NF-kappaB proinfammatory responses. J Biol Chem. 2009 Sep 4;284(36):24192-24203.
62. Albrecht V, Hofer TP, Foxwell B, Frankenberger M, Ziegler-Heitbrock L. Tolerance induced via TLR2 and TLR4 in human dendritic cells: role of IRAK-1. BMC Immunol. 2008;9:69.
63. Huang YS, Misior A, Li LW. Novel role and regulation of the interleukin-1 receptor associated kinase (IRAK) family proteins. Cell Mol Immunol. 2005 Feb;2(1):36-39.
64. Janssens S, Beyaert R. Functional diversity and regulation of diferent interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell. 2003 Feb;11(2):293-302.
65. Keating SE, Maloney GM, Moran EM, Bowie AG. IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination. J Biol Chem. 2007 Nov 16;282(46):33435-33443.
66. Motshwene PG, Moncriefe MC, Grossmann JG, Kao C, Ayaluru M, Sandercock AM, Robinson CV, Latz E, Gay NJ. An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4. J Biol Chem. 2009 Sep 11;284(37):25404-25411.
67. ONeill LA, Dunne A, Edjeback M, Gray P, Jeferies C, Wietek C. Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors. J Endotoxin Res. 2003;9(1):55-59.
68. Schilling D, Tomas K, Nixdorf K, Vogel SN, Fenton MJ. Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid diferentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages. J Immunol. 2002 Nov 15;169(10):5874-5880.
69. Suzuki N, Suzuki S, Yeh WC. IRAK-4 as the central TIR signaling mediator in innate immunity. Trends Immunol. 2002 Oct;23(10):503-506.
70. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, Takeda K, Akira S. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002 Nov 21;420(6913):324-329.
71. Lang T, Mansell A. Te negative regulation of Tolllike receptor and associated pathways. Immunol Cell Biol. 2007 Aug-Sep;85(6):425-434.
72. Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG. Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat Immunol. 2000 Dec;1(6):533-540.
73. Chaudhary A, Fresquez TM, Naranjo MJ. Tyrosine kinase Syk associates with toll-like receptor 4 and regulates signaling in human monocytic cells. Immunol Cell Biol. 2007 Apr-May;85(3):249-256.
74. Gohda J, Matsumura T, Inoue J. Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling. J Immunol. 2004 Sep 1;173(5):2913-2917.
75. Carmody RJ, Chen YH. Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. Cell Mol Immunol. 2007 Feb;4(1):31-41.
76. Karaghiosof M, Steinborn R, Kovarik P, Kriegshäuser G, Baccarini M, Donabauer B, Reichart U, Kolbe T,. Bogdan C, Leanderson T, Levy D, Decker T, Müller M. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003 May;4(5):471-477.
77. Zhang FX, Kirschning CJ, Mancinelli R, Xu XP, Jin Y, Faure E, Mantovani A, Rothe M, Muzio M, Arditi M. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem. 1999 Mar 19;274(12):7611-7614.
78. Rowlett RM, Chrestensen CA, Nyce M, Harp MG, Pelo JW, Cominelli F, Ernst PB, Pizarro TT, Sturgill TW, Worthington MT. MNK kinases regulate multiple TLR pathways and innate proinfammatory cytokines in macrophages. Am J Physiol Gastrointest Liver Physiol. 2008 Feb;294(2):G452-9.
79. Fasciano S, Li L. Intervention of Toll-like receptor-mediated human innate immunity and infammation by synthetic compounds and naturally occurring products. Curr Med Chem. 2006;13(12):1389-1395.
80. Toshchakov VY, Vogel SN. Cell-penetrating TIR BB loop decoy peptides a novel class of TLR signaling inhibitors and a tool to study topology of TIR-TIR interactions. Expert Opin Biol Ter. 2007 Jul;7(7):1035-1050.
81. Noman AS, Koide N, Hassan F, I-E-Khuda I, Dagvadorj J, Tumurkhuu G, Islam S, Naiki Y, Yoshida T, Yokochi T. Talidomide inhibits lipopolysaccharide- induced tumor necrosis factor-alpha production via down-regulation of MyD88 expression. Innate Immun. 2009 Feb;15(1):33-41.
82. Buckley GM, Fosbeary R, Fraser JL, Gowers L, Higueruelo AP, James LA, Jenkins K, Mack SR, Morgan T, Parry DM, Pitt WR, Rausch O, Richard MD, Sabin V. IRAK-4 inhibitors. Part III: a series of imidazo[1,2-a]pyridines. Bioorg Med Chem Lett. 2008 Jun 15;18(12):3656-3660
83. Peptide Inhibitors under research tools pp 1-12 [database on the Internet]. Available from: www.imgenex.com/inhibitors.php.
84. Wang Z, Wesche H, Stevens T, Walker N, Yeh WC. IRAK-4 inhibitors for infammation. Curr Top Med Chem. 2009;9(8):724-737.
85. Scapin G. Protein kinase inhibition: different approaches to selective inhibitor design. Curr Drug Targets. 2006 Nov;7(11):1443-1454.
86. Youn HS, Lee JY, Fitzgerald KA, Young HA, Akira S, Hwang DH. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol. 2005 Sep 1;175(5):3339-3346.
87. ONeill LA, Bryant CE, Doyle SL. Terapeutic targeting of toll-like receptors for infectious and infammatory diseases and cancer. Pharmacol Rev. 2009 Jun;61(2):177-197.
88. Liu Y, Yu H, Zhang Y, Zhao Y. TLRs are important infammatory factors in atherosclerosis and may be a therapeutic target. Med Hypotheses. 2008;70(2):314-316.
89. Kim JH, Jeong JH, Jeon ST, Kim H, Ock J, Suk K, Kim SI, Song KS, Lee WH. Decursin inhibits induction of infammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol Pharmacol. 2006 Jun;69(6):1783-1790.
90. Guedat P, Colland F. Patented small molecule inhibitors in the ubiquitin proteasome system. BMC Biochem. 2007;8(Suppl 1):S14.
91. Reis J, Tan X, Yang R, Rockwell CE, Papasian CJ, Vogel SN, Morrison DC, Qureshi AA, Qureshi N. A combination of proteasome inhibitors and antibiotics prevents lethality in a septic shock model. Innate Immun. 2008 Oct;14(5):319-329.
92. Salminen A, Lehtonen M, Suuronen T, Kaarniranta K, Huuskonen J. Terpenoids: natural inhibitors of NF-kappaB signaling with anti-infammatory and anticancer potential. Cell Mol Life Sci. 2008 Oct;65(19):2979-2999.
93. Tsuchida K, Chaki H, Takakura T, Kotsubo H, Tanaka T, Aikawa Y, Shiozawa S, Hirono S. Discovery of nonpeptidic small-molecule AP-1 inhibitors: lead hopping based on a three-dimensional pharmacophore model. J Med Chem. 2006 Jan 12;49(1):80-91.
94. Tsuchida K, Chaki H, Takakura T, Yokotani J, Aikawa Y, Shiozawa S, Gouda H, Hirono S. Design, synthesis, and biological evaluation of new cyclic disulfde deca-peptides that inhibit the binding of AP-1 to DNA. J Med Chem. 2004 Aug 12;47(17):4239-4246.
95. Ahn JY, Choi IS, Shim JY, Yun EK, Yun YS, Jeong G, Song JY. Te immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Tolllike receptor-mediated infammatory signals. Eur J Immunol. 2006 Jan;36(1):37-45.
96. Chou TC. Anti-infammatory and analgesic efects of paeonol in carrageenan-evoked thermal hyperalgesia. Br J Pharmacol. 2003 Jul;139(6):1146-1152.
97. Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, Finberg RW, Tarakhovsky A, Vogel SN, Belkaid Y, Kurt-Jones EA, Karp CL. Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat Immunol. 2005 Jun;6(6):571-578.
98. Zhande R, Dauphinee SM, Tomas JA, Yamamoto M, Akira S, Karsan A. FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Mol Cell Biol. 2007 Nov;27(21):7394-7404.
99. Kobayashi T, Walsh MC, Choi Y. Te role of TRAF6 in signal transduction and the immune response. Microbes Infect. 2004 Nov;6(14):1333-1338.
100. Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A. Homeostatic MyD88-dependent signals cause lethal infamMation in the absence of A20. J Exp Med. 2008 Feb 18;205(2):451-464.
101. Li HY, Liu H, Wang CH, Zhang JY, Man JH, Gao YF, Zhang PJ, Li WH, Zhao J, Pan X, Zhou T, Gong WL, Li AL, Zhang XM. Deactivation of the kinase IKK by CUEDC2 through recruitment of the phos-phatase PP1. Nat Immunol. 2008 May;9(5):533-541.
102. Siepe D, Jentsch S. Prolyl isomerase Pin1 acts as a switch to control the degree of substrate ubiquityla-tion. Nat Cell Biol. 2009 Aug;11(8):967-972.
103. Almeida PE, Silva AR, Maya-Monteiro CM, Töröcsik D, DAvila H, Dezsö B, Magalhães KG, Castro-Faria-Neto HC, Nagy L, Bozza P T. Mycobacterium bovis bacillus Calmette-Guerin infection induces TLR2-dependent peroxisome proliferator-activated receptor gamma expression and activation: functions in infammation, lipid metabolism, and pathogenesis. J Immunol. 2009 Jul 15;183(2):1337-1345.
104. Wullaert A, Verstrepen L, Van Hufel S, Adib-Conquy M, Cornelis S, Kreike M, Haegman M, El Bakkouri K, Sanders M, Verhelst K, Carpentier I, Cavaillon JM, Heyninck K, Beyaert R. LIND/ABIN-3 is a novel lipopolysaccharide-inducible inhibitor of NF-kappaB activation. J Biol Chem. 2007 Jan 5;282(1):81-90.
105. Kurdi M, Booz GW. Can the protective actions of JAK-STAT in the heart be exploited therapeuti-cally? Parsing the regulation of interleukin-6-type cytokine signaling. J Cardiovasc Pharmacol. 2007 Aug;50(2):126-141.
106. Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007 Mar 1;178(5):2623-2629.
107. Ortiz-Muñoz G, Martin-Ventura JL, Hernandez-Vargas P, Mallavia B, Lopez-Parra V, Lopez-Franco O, Muñoz-Garcia B, Fernandez-Vizarra P, Ortega L, Egido J, Gomez-Guerrero C. Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis. Arterioscler Tromb Vasc Biol. 2009 Apr;29(4):525-531.
108. Johnston JA. Are SOCS suppressors, regulators, and degraders? J Leukoc Biol. 2004 May;75(5):743-748.
109. Veeriah S, Brennan C, Meng S, Singh B, Fagin JA, Solit DB, Paty PB, Rohle D, Vivanco I, Chmielecki J, Pao W, Ladanyi M, Gerald WL, Liau L, Cloughesy TC, Mischel PS, Sander C, Taylor B, Schultz N, Major J, Heguy A, Fang F, Mellinghof IK, Chan TA. Te tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci USA. 2009 Jun 9;106(23):9435-9440.
110. El Kasmi KC, Holst J, Cofre M, Mielke L, de Pauw A, Lhocine N, Smith AM, Rutschman R, Kaushal D, Shen Y, Suda T, Donnelly RP, Myers MG Jr, Alexander W, Vignali DA, Watowich SS, Ernst M, Hilton DJ, Murray PJ. General nature of the STAT3-activated anti-infammatory response. J Immunol. 2006 Dec 1;177(11):7880-7888.
111. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003 Aug 15;374(Pt 1):1-20.
112. Li CH, Wang JH, Redmond HP. Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation. J Leukoc Biol. 2006 Apr;79(4):867-875.
113. Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Cofman RL, Liu YJ, Barrat FJ, Soumelis V. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid pre-dendritic cells in response to TLR activation. J Exp Med. 2008 Feb 18;205(2):315-322.
114. Murray PJ. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-infammatory response. Curr Opin Pharmacol. 2006 Aug;6(4):379-386.
115. Blanco P, Palucka AK, Pascual V, Banchereau J. Dendritic cells and cytokines in human infammatory and autoimmune diseases. Cytokine Growth Factor Rev. 2008 Feb;19(1):41-52.
116. Decker T. Sepsis: avoiding its deadly toll. J Clin Invest. 2004 May;113(10):1387-1389.
117. Toubi E, Shoenfeld Y. Toll-like receptors and their role in the development of autoimmune diseases. Autoimmunity. 2004 May;37(3):183-188.