Skip to main content

Advertisement

SpringerLink
Log in

NOX enzymes and Toll-like receptor signaling

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Invading microorganisms are recognized by the host innate immune system through pattern recognition receptors. Among these receptors, Toll-like receptors (TLRs) are able to sense the molecular signatures of microbial pathogens, protozoa, fungi, and virus and activate proinflammatory signaling cascades. In addition to their role in bacterial killing by phagocytes, reactive oxygen species generated by NADPH oxidase (NOX) homologues also play key roles in signaling and host defense in a variety of cell types. Recent studies have demonstrated a link between TLR activation and NOX homologues following microbial recognition highlighting their important role in the innate immune response and host defense.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ago T, Kitazono T, Ooboshi H, Iyama T, Han YH, Takada J, Wakisaka M, Ibayashi S, Utsumi H, Iida M (2004) Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 109:227–233

    Article  PubMed  CAS  Google Scholar 

  2. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Article  PubMed  CAS  Google Scholar 

  3. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738

    Article  PubMed  CAS  Google Scholar 

  4. Ambasta RK, Kumar P, Griendling KK, Schmidt HH, Busse R, Brandes RP (2004) Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J Biol Chem 279:45935–45941

    Article  PubMed  CAS  Google Scholar 

  5. Ameziane-El-Hassani R, Morand S, Boucher JL, Frapart YM, Apostolou D, Agnandji D, Gnidehou S, Ohayon R, Noel-Hudson MS, Francon J, Lalaoui K, Virion A, Dupuy C (2005) Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. J Biol Chem 280:30046–30054

    Article  PubMed  CAS  Google Scholar 

  6. Asehnoune K, Strassheim D, Mitra S, Kim JY, Abraham E (2004) Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappa B. J Immunol 172:2522–2529

    PubMed  CAS  Google Scholar 

  7. Babior BM (1999) NADPH oxidase: an update. Blood 93:1464–1476

    PubMed  CAS  Google Scholar 

  8. Babior BM, Lambeth JD, Nauseef W (2002) The neutrophil NADPH oxidase. Arch Biochem Biophys 397:342–344

    Article  PubMed  CAS  Google Scholar 

  9. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179

    Article  PubMed  CAS  Google Scholar 

  10. Banfi B, Maturana A, Jaconi S, Arnaudeau S, Laforge T, Sinha B, Ligeti E, Demaurex N, Krause KH (2000) A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287:138–142

    Article  PubMed  CAS  Google Scholar 

  11. Banfi B, Clark RA, Steger K, Krause KH (2003) Two novel proteins activate superoxide generation by the NADPH oxidase NOX1. J Biol Chem 278:3510–3513

    Article  PubMed  CAS  Google Scholar 

  12. Banfi B, Malgrange B, Knisz J, Steger K, Dubois-Dauphin M, Krause KH (2004) NOX3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem 279:46065–46072

    Article  PubMed  CAS  Google Scholar 

  13. Banfi B, Tirone F, Durussel I, Knisz J, Moskwa P, Molnar GZ, Krause KH, Cox JA (2004) Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J Biol Chem 279:18583–18591

    Article  PubMed  CAS  Google Scholar 

  14. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313

    Article  PubMed  CAS  Google Scholar 

  15. Burg ND, Pillinger MH (2001) The neutrophil: function and regulation in innate and humoral immunity. Clin Immunol 99:7–17

    Article  PubMed  CAS  Google Scholar 

  16. Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD (2001) Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269:131–140

    Article  PubMed  CAS  Google Scholar 

  17. Cheng G, Ritsick D, Lambeth JD (2004) Nox3 regulation by NOXO1, p47phox, and p67phox. J Biol Chem 279:34250–34255

    Article  PubMed  CAS  Google Scholar 

  18. Cheng G, Diebold BA, Hughes Y, Lambeth JD (2006) Nox1-dependent reactive oxygen generation is regulated by Rac1. J Biol Chem 281:17718–17726

    Article  PubMed  CAS  Google Scholar 

  19. Chiang E, Dang O, Anderson K, Matsuzawa A, Ichijo H, David M (2006) Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide. J Immunol 176:5720–5724

    PubMed  CAS  Google Scholar 

  20. Chuang T, Ulevitch RJ (2001) Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim Biophys Acta 1518:157–161

    PubMed  CAS  Google Scholar 

  21. Cucoranu I, Clempus R, Dikalova A, Phelan PJ, Ariyan S, Dikalov S, Sorescu D (2005) NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97:900–907

    Article  PubMed  CAS  Google Scholar 

  22. De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F (2000) Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem 275:23227–23233

    Article  PubMed  Google Scholar 

  23. DeLeo FR, Quinn MT (1996) Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins. J Leukoc Biol 60:677–691

    PubMed  Google Scholar 

  24. DeLeo FR, Renee J, McCormick S, Nakamura M, Apicella M, Weiss JP, Nauseef WM (1998) Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly. J Clin Invest 101:455–463

    Article  PubMed  CAS  Google Scholar 

  25. Dupuy C, Ohayon R, Valent A, Noel-Hudson MS, Deme D, Virion A (1999) Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs. J Biol Chem 274:37265–37269

    Article  PubMed  CAS  Google Scholar 

  26. el Benna J, Faust LP, Babior BM (1994) The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. J Biol Chem 269:23431–23436

    PubMed  Google Scholar 

  27. El Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D, Ohayon R, Kaniewski J, Noel-Hudson MS, Bidart JM, Schlumberger M, Virion A, Dupuy C (2005) Dual oxidase2 is expressed all along the digestive tract. Am J Physiol Gastrointest Liver Physiol 288:G933–G942

    Article  PubMed  CAS  Google Scholar 

  28. Fan J, Frey RS, Malik AB (2003) TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase. J Clin Invest 112:1234–1243

    PubMed  CAS  Google Scholar 

  29. Fan J, Li Y, Levy RM, Fan JJ, Hackam DJ, Vodovotz Y, Yang H, Tracey KJ, Billiar TR, Wilson MA (2007) Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1–TLR4 signaling. J Immunol 178:6573–6580

    PubMed  CAS  Google Scholar 

  30. Forteza R, Salathe M, Miot F, Conner GE (2005) Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol 32:462–469

    Article  PubMed  CAS  Google Scholar 

  31. Frantz S, Kelly RA, Bourcier T (2001) Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. J Biol Chem 276:5197–5203

    Article  PubMed  CAS  Google Scholar 

  32. Gao XP, Standiford TJ, Rahman A, Newstead M, Holland SM, Dinauer MC, Liu QH, Malik AB (2002) Role of NADPH oxidase in the mechanism of lung neutrophil sequestration and microvessel injury induced by Gram-negative sepsis: studies in p47phox−/− and gp91phox−/− mice. J Immunol 168:3974–3982

    PubMed  CAS  Google Scholar 

  33. Geiszt M, Kopp JB, Varnai P, Leto TL (2000) Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci USA 97:8010–8014

    Article  PubMed  CAS  Google Scholar 

  34. Geiszt M, Lekstrom K, Brenner S, Hewitt SM, Dana R, Malech HL, Leto TL (2003) NAD(P)H oxidase 1, a product of differentiated colon epithelial cells, can partially replace glycoprotein 91phox in the regulated production of superoxide by phagocytes. J Immunol 171:299–306

    PubMed  CAS  Google Scholar 

  35. Geiszt M, Lekstrom K, Witta J, Leto TL (2003) Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells. J Biol Chem 278:20006–20012

    Article  PubMed  CAS  Google Scholar 

  36. Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL (2003) Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J 17:1502–1504

    PubMed  CAS  Google Scholar 

  37. Geiszt M (2006) NADPH oxidases: new kids on the block. Cardiovasc Res 71:289–299

    Article  PubMed  CAS  Google Scholar 

  38. Ha EM, Oh CT, Bae YS, Lee WJ (2005) A direct role for dual oxidase in Drosophila gut immunity. Science 310:847–850

    Article  PubMed  CAS  Google Scholar 

  39. Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, Setiadi H, Wu R (2005) Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBS Lett 579:4911–4917

    Article  PubMed  CAS  Google Scholar 

  40. Hartl D, Lehmann N, Hoffmann F, Jansson A, Hector A, Notheis G, Roos D, Belohradsky BH, Wintergerst U (2008) Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease. J Allergy Clin Immunol 121(2):375–382

    Article  PubMed  CAS  Google Scholar 

  41. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099–1103

    Article  PubMed  CAS  Google Scholar 

  42. Hayashi F, Means TK, Luster AD (2003) Toll-like receptors stimulate human neutrophil function. Blood 102:2660–2669

    Article  PubMed  CAS  Google Scholar 

  43. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    Article  PubMed  CAS  Google Scholar 

  44. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745

    Article  PubMed  CAS  Google Scholar 

  45. Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, Griendling KK (2004) Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 24:677–683

    Article  PubMed  CAS  Google Scholar 

  46. Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A (2002) Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 195:559–570

    Article  PubMed  CAS  Google Scholar 

  47. Hornef MW, Normark BH, Vandewalle A, Normark S (2003) Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells. J Exp Med 198:1225–1235

    Article  PubMed  CAS  Google Scholar 

  48. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995

    Article  PubMed  CAS  Google Scholar 

  49. Jackson SH, Gallin JI, Holland SM (1995) The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med 182:751–758

    Article  PubMed  CAS  Google Scholar 

  50. Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11:293–302

    Article  PubMed  CAS  Google Scholar 

  51. Katsuyama M, Fan C, Yabe-Nishimura C (2002) NADPH oxidase is involved in prostaglandin F2alpha-induced hypertrophy of vascular smooth muscle cells: induction of NOX1 by PGF2alpha. J Biol Chem 277:13438–13442

    Article  PubMed  CAS  Google Scholar 

  52. Katsuyama M, Fan C, Arakawa N, Nishinaka T, Miyagishi M, Taira K, Yabe-Nishimura C (2005) Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH oxidase: involvement of mitochondrial respiratory chain. Biochem J 386:255–261

    Article  PubMed  CAS  Google Scholar 

  53. Kawahara T, Kuwano Y, Teshima-Kondo S, Takeya R, Sumimoto H, Kishi K, Tsunawaki S, Hirayama T, Rokutan K (2004) Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells. J Immunol 172:3051–3058

    PubMed  CAS  Google Scholar 

  54. Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, Tsunawaki S, Wada A, Sumimoto H, Rokutan K (2005) Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol Cell Physiol 288:C450–C457

    Article  PubMed  CAS  Google Scholar 

  55. Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19:24–32

    Article  PubMed  CAS  Google Scholar 

  56. Kishimoto K, Matsumoto K, Ninomiya-Tsuji J (2000) TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J Biol Chem 275:7359–7364

    Article  PubMed  CAS  Google Scholar 

  57. Kiss PJ, Knisz J, Zhang Y, Baltrusaitis J, Sigmund CD, Thalmann R, Smith RJ, Verpy E, Banfi B (2006) Inactivation of NADPH oxidase organizer 1 results in severe imbalance. Curr Biol 16:208–213

    Article  PubMed  CAS  Google Scholar 

  58. Kobayashi SD, Voyich JM, Burlak C, DeLeo FR (2005) Neutrophils in the innate immune response. Arch Immunol Ther Exp (Warsz) 53:505–517

    CAS  Google Scholar 

  59. Koff JL, Shao MX, Kim S, Ueki IF, Nadel JA (2006) Pseudomonas lipopolysaccharide accelerates wound repair via activation of a novel epithelial cell signaling cascade. J Immunol 177:8693–8700

    PubMed  CAS  Google Scholar 

  60. Kusumoto K, Kawahara T, Kuwano Y, Teshima-Kondo S, Morita K, Kishi K, Rokutan K (2005) Ecabet sodium inhibits Helicobacter pylori lipopolysaccharide-induced activation of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells. Am J Physiol Gastrointest Liver Physiol 288:G300–G307

    Article  PubMed  CAS  Google Scholar 

  61. Kuwano Y, Kawahara T, Yamamoto H, Teshima-Kondo S, Tominaga K, Masuda K, Kishi K, Morita K, Rokutan K (2006) Interferon-gamma activates transcription of NADPH oxidase 1 gene and upregulates production of superoxide anion by human large intestinal epithelial cells. Am J Physiol Cell Physiol 290:C433–C443

    Article  PubMed  CAS  Google Scholar 

  62. Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    Article  PubMed  CAS  Google Scholar 

  63. Laroux FS, Romero X, Wetzler L, Engel P, Terhorst C (2005) Cutting edge: MyD88 controls phagocyte NADPH oxidase function and killing of gram-negative bacteria. J Immunol 175:5596–5600

    PubMed  CAS  Google Scholar 

  64. Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK (2001) Novel gp91(phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res 88:888–894

    Article  PubMed  CAS  Google Scholar 

  65. Lee JG, Lee SH, Park DW, Yoon HS, Chin BR, Kim JH, Kim JR, Baek SH (2008) Toll-like receptor 9-stimulated monocyte chemoattractant protein-1 is mediated via JNK-cytosolic phospholipase A(2)-ROS signaling. Cell Signal 20:105–111

    Article  PubMed  CAS  Google Scholar 

  66. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973–983

    Article  PubMed  CAS  Google Scholar 

  67. Li S, Strelow A, Fontana EJ, Wesche H (2002) IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci USA 99:5567–5572

    Article  PubMed  CAS  Google Scholar 

  68. Lin FY, Chen YH, Lin YW, Tsai JS, Chen JW, Wang HJ, Chen YL, Li CY, Lin SJ (2006) The role of human antigen R, an RNA-binding protein, in mediating the stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel mechanism involved in vascular inflammation. Arterioscler Thromb Vasc Biol 26:2622–2629

    Article  PubMed  CAS  Google Scholar 

  69. Lin FY, Chen YH, Tasi JS, Chen JW, Yang TL, Wang HJ, Li CY, Chen YL, Lin SJ (2006) Endotoxin induces toll-like receptor 4 expression in vascular smooth muscle cells via NADPH oxidase activation and mitogen-activated protein kinase signaling pathways. Arterioscler Thromb Vasc Biol 26:2630–2637

    Article  PubMed  CAS  Google Scholar 

  70. Matsuzawa A, Saegusa K, Noguchi T, Sadamitsu C, Nishitoh H, Nagai S, Koyasu S, Matsumoto K, Takeda K, Ichijo H (2005) ROS-dependent activation of the TRAF6–ASK1–p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6:587–592

    Article  PubMed  CAS  Google Scholar 

  71. McPhail LC, Clayton CC, Snyderman R (1984) The NADPH oxidase of human polymorphonuclear leukocytes. Evidence for regulation by multiple signals. J Biol Chem 259:5768–5775

    PubMed  CAS  Google Scholar 

  72. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397

    Article  PubMed  CAS  Google Scholar 

  73. Medzhitov R, Janeway C Jr. (2000) The Toll receptor family and microbial recognition. Trends Microbiol 8:452–456

    Article  PubMed  CAS  Google Scholar 

  74. Miletic AV, Graham DB, Montgrain V, Fujikawa K, Kloeppel T, Brim K, Weaver B, Schreiber R, Xavier R, Swat W (2007) Vav proteins control MyD88-dependent oxidative burst. Blood 109:3360–3368

    Article  PubMed  CAS  Google Scholar 

  75. Morand S, Dos Santos OF, Ohayon R, Kaniewski J, Noel-Hudson MS, Virion A, Dupuy C (2003) Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes. Endocrinology 144:567–574

    Article  PubMed  CAS  Google Scholar 

  76. Morgenstern DE, Gifford MA, Li LL, Doerschuk CM, Dinauer MC (1997) Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med 185:207–218

    Article  PubMed  CAS  Google Scholar 

  77. Nakahira K, Kim HP, Geng XH, Nakao A, Wang X, Murase N, Drain PF, Sasidhar M, Nabel EG, Takahashi T, Lukacs NW, Ryter SW, Morita K, Choi AM (2006) Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts. J Exp Med 203:2377–2389

    Article  PubMed  CAS  Google Scholar 

  78. Nakano Y, Banfi B, Jesaitis AJ, Dinauer MC, Allen LA, Nauseef WM (2007) Critical roles for p22phox in the structural maturation and subcellular targeting of Nox3. Biochem J 403:97–108

    Article  PubMed  CAS  Google Scholar 

  79. Neal MD, Leaphart C, Levy R, Prince J, Billiar TR, Watkins S, Li J, Cetin S, Ford H, Schreiber A, Hackam DJ (2006) Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol 176:3070–3079

    PubMed  CAS  Google Scholar 

  80. Ortega-Cava CF, Ishihara S, Rumi MA, Kawashima K, Ishimura N, Kazumori H, Udagawa J, Kadowaki Y, Kinoshita Y (2003) Strategic compartmentalization of Toll-like receptor 4 in the mouse gut. J Immunol 170:3977–3985

    PubMed  CAS  Google Scholar 

  81. Pacquelet S, Johnson JL, Ellis BA, Brzezinska AA, Lane WS, Munafo DB, Catz SD (2007) Cross-talk between IRAK-4 and the NADPH oxidase. Biochem J 403:451–461

    Article  PubMed  CAS  Google Scholar 

  82. Paffenholz R, Bergstrom RA, Pasutto F, Wabnitz P, Munroe RJ, Jagla W, Heinzmann U, Marquardt A, Bareiss A, Laufs J, Russ A, Stumm G, Schimenti JC, Bergstrom DE (2004) Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev 18:486–491

    Article  PubMed  CAS  Google Scholar 

  83. Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS (2004) Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol 173:3589–3593

    PubMed  CAS  Google Scholar 

  84. Park HS, Chun JN, Jung HY, Choi C, Bae YS (2006) Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells. Cardiovasc Res 72:447–455

    Article  PubMed  CAS  Google Scholar 

  85. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279:7370–7377

    Article  PubMed  CAS  Google Scholar 

  86. Patel DN, Bailey SR, Gresham JK, Schuchman DB, Shelhamer JH, Goldstein BJ, Foxwell BM, Stemerman MB, Maranchie JK, Valente AJ, Mummidi S, Chandrasekar B (2006) TLR4–NOX4–AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells. Biochem Biophys Res Commun 347:1113–1120

    Article  PubMed  CAS  Google Scholar 

  87. Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C, Marie JC, Pouzet C, Samadi M, Elbim C, O’Dowd Y, Bens M, Vandewalle A, Gougerot-Pocidalo MA, Lizard G, Ogier-Denis E (2004) NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24:10703–10717

    Article  PubMed  CAS  Google Scholar 

  88. Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299:2076–2079

    Article  PubMed  CAS  Google Scholar 

  89. Picard C, von Bernuth H, Ku CL, Yang K, Puel A, Casanova JL (2007) Inherited human IRAK-4 deficiency: an update. Immunol Res 38:347–352

    Article  PubMed  CAS  Google Scholar 

  90. Pollock JD, Williams DA, Gifford MA, Li LL, Du X, Fisherman J, Orkin SH, Doerschuk CM, Dinauer MC (1995) Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet 9:202–209

    Article  PubMed  CAS  Google Scholar 

  91. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    Article  PubMed  CAS  Google Scholar 

  92. Schwarzer C, Machen TE, Illek B, Fischer H (2004) NADPH oxidase-dependent acid production in airway epithelial cells. J Biol Chem 279:36454–36461

    Article  PubMed  CAS  Google Scholar 

  93. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    Article  PubMed  CAS  Google Scholar 

  94. Segal BH, Doherty TM, Wynn TA, Cheever AW, Sher A, Holland SM (1999) The p47(phox−/−) mouse model of chronic granulomatous disease has normal granuloma formation and cytokine responses to Mycobacterium avium and Schistosoma mansoni eggs. Infect Immun 67:1659–1665

    PubMed  CAS  Google Scholar 

  95. Sengelov H (1995) Complement receptors in neutrophils. Crit Rev Immunol 15:107–131

    PubMed  CAS  Google Scholar 

  96. Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, Hattori M, Sakaki Y, Sumimoto H (2001) A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem 276:1417–23

    Article  PubMed  CAS  Google Scholar 

  97. Smiley ST, King JA, Hancock WW (2001) Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 167:2887–2894

    PubMed  CAS  Google Scholar 

  98. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401:79–82

    Article  PubMed  CAS  Google Scholar 

  99. Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9

    Article  PubMed  CAS  Google Scholar 

  100. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14

    Article  PubMed  CAS  Google Scholar 

  101. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940

    Article  PubMed  CAS  Google Scholar 

  102. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14

    PubMed  CAS  Google Scholar 

  103. Takeya R, Ueno N, Kami K, Taura M, Kohjima M, Izaki T, Nunoi H, Sumimoto H (2003) Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. J Biol Chem 278:25234–25246

    Article  PubMed  CAS  Google Scholar 

  104. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC (2002) Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 195:99–111

    Article  PubMed  CAS  Google Scholar 

  105. Teshima S, Kutsumi H, Kawahara T, Kishi K, Rokutan K (2000) Regulation of growth and apoptosis of cultured guinea pig gastric mucosal cells by mitogenic oxidase 1. Am J Physiol Gastrointest Liver Physiol 279:G1169–G1176

    PubMed  CAS  Google Scholar 

  106. Ueno N, Takeya R, Miyano K, Kikuchi H, Sumimoto H (2005) The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem 280:23328–23339

    Article  PubMed  CAS  Google Scholar 

  107. Ueyama T, Geiszt M, Leto TL (2006) Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases. Mol Cell Biol 26:2160–2174

    Article  PubMed  CAS  Google Scholar 

  108. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H (2002) HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 277:15107–15112

    Article  PubMed  CAS  Google Scholar 

  109. Vaquero EC, Edderkaoui M, Pandol SJ, Gukovsky I, Gukovskaya AS (2004) Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells. J Biol Chem 279:34643–34654

    Article  PubMed  CAS  Google Scholar 

  110. Vignais PV (2002) The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 59:1428–1459

    Article  PubMed  CAS  Google Scholar 

  111. Vulcano M, Dusi S, Lissandrini D, Badolato R, Mazzi P, Riboldi E, Borroni E, Calleri A, Donini M, Plebani A, Notarangelo L, Musso T, Sozzani S (2004) Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells. J Immunol 173:5749–5756

    PubMed  CAS  Google Scholar 

  112. Wang D, De Deken X, Milenkovic M, Song Y, Pirson I, Dumont JE, Miot F (2005) Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. J Biol Chem 280:3096–3103

    Article  PubMed  CAS  Google Scholar 

  113. Ward RA, Nakamura M, McLeish KR (2000) Priming of the neutrophil respiratory burst involves p38 mitogen-activated protein kinase-dependent exocytosis of flavocytochrome b558-containing granules. J Biol Chem 275:36713–36719

    Article  PubMed  CAS  Google Scholar 

  114. Werling D, Jungi TW (2003) TOLL-like receptors linking innate and adaptive immune response. Vet Immunol Immunopathol 91:1–12

    Article  PubMed  CAS  Google Scholar 

  115. Wingler K, Wunsch S, Kreutz R, Rothermund L, Paul M, Schmidt HH (2001) Up-regulation of the vascular NAD(P)H-oxidase isoforms Nox1 and Nox4 by the renin–angiotensin system in vitro and in vivo. Free Radic Biol Med 31:1456–1464

    Article  PubMed  CAS  Google Scholar 

  116. Yang S, Zhang Y, Ries W, Key L (2004) Expression of Nox4 in osteoclasts. J Cell Biochem 92:238–248

    Article  PubMed  CAS  Google Scholar 

  117. Zhang X, Shan P, Jiang G, Cohn L, Lee PJ (2006) Toll-like receptor 4 deficiency causes pulmonary emphysema. J Clin Invest 116:3050–3059

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Financial support was from the Institut National de la Santé et de la Recherche Médicale (INSERM) and in part by grants from the Association François Aupetit AFA, the Ligue Nationale contre le Cancer, the Feering and Ypsen Laboratories, and the Société Nationale Française de Gastro-entérologie (SNFGE) and the Association Française pour l’étude du foie (AFEF) for the Programme National de Recherche en Hépato-Gastroentérologie (PNRHGE 2007/2008 INSERM). Sanae Ben Mkaddem was supported by a Ph.D. student’s grant from the Ligue Nationale contre le Cancer.

Author information

Authors and Affiliations

  1. INSERM, U773, Centre de Recherche Biomédicale Bichat Beaujon, CRB3, BP 416, 75018, Paris, France

    Eric Ogier-Denis, Sanae Ben Mkaddem & Alain Vandewalle

  2. Université Paris 7-Denis Diderot, site Bichat, BP 416, 75870, Paris, France

    Eric Ogier-Denis, Sanae Ben Mkaddem & Alain Vandewalle

Authors
  1. Eric Ogier-Denis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanae Ben Mkaddem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alain Vandewalle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric Ogier-Denis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogier-Denis, E., Mkaddem, S.B. & Vandewalle, A. NOX enzymes and Toll-like receptor signaling. Semin Immunopathol 30, 291–300 (2008). https://doi.org/10.1007/s00281-008-0120-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-008-0120-9

Keywords

Search

Navigation