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Infektion und Entzündung

  • Rudolf A. Rupec
Conference paper
Part of the Fortschritte der praktischen Dermatologie und Venerologie book series (DERMATOLOGIE, volume 18)

Zusammenfassung

Überwinden pathogene Mikroorganismen eine körpereigene Barriere, wird ein pathophysiologischer Prozess in Gang gesetzt, der zur ihrer Beseitigung führt: die Entzündung. Im folgenden Kapitel sollen die Möglichkeiten von Wirtszellen aufgezeigt werden, Mikroorganismen zu erkennen. Darüber hinaus werden die intrazellulären Mechanismen vorgestellt, die als Folge dieser Erkennung aktiviert werden. Die Funktionen von Chemokinen und Chemokinrezeptoren sowie von Adhäsionsmolekülen bei der Entzündung werden in gesonderten Kapiteln in diesem Band behandelt.

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Literatur

  1. 1.
    Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413: 732–738PubMedCrossRefGoogle Scholar
  2. 2.
    Baeuerle PA, Henkel T (1994) Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141–179PubMedCrossRefGoogle Scholar
  3. 3.
    Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–252PubMedCrossRefGoogle Scholar
  4. 4.
    Belvin MP, Anderson KV (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Dev Biol 12: 393–416PubMedCrossRefGoogle Scholar
  5. 5.
    Cao Z, Henzel WJ, Gao X (1996) IRAK: a kinase associated with the interleukin-1 receptor. Science 271:1128–1131PubMedCrossRefGoogle Scholar
  6. 6.
    Cavigelli M, Dolfì F, Claret FX, Karin M (1995) Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J 14: 5957–5964PubMedCentralPubMedGoogle Scholar
  7. 7.
    Chu WM, Ostertag D, Li ZW, Chang L, Chen Y, Hu Y, Williams B, Perrault J, Karin M (1999) JNK2 and IKKß are required for activating the innate response to viral infection. Immunity 11:721–731PubMedCrossRefGoogle Scholar
  8. 8.
    Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103: 239–252PubMedCrossRefGoogle Scholar
  9. 9.
    Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara JL (2001) Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167: 1882–1885PubMedCrossRefGoogle Scholar
  10. 10.
    Gewirtz AT, Simon PO jr, Schmitt CK, Taylor LJ, Hagedorn CH, O’Brien AD, Neish AS, Madara JL (2001) Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J Clin Invest 107:99–109PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Ghosh S, Karin M (2002) Missing pieces in the NF-κB puzzle. Cell 109 [suppl]: S81–96PubMedCrossRefGoogle Scholar
  12. 12.
    Hacker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H (1998) CpG-DNA-specifìc activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J 17: 6230–6240PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Hashimoto C, Hudson KL, Anderson KV (1988) The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 52:269–279PubMedCrossRefGoogle Scholar
  14. 14.
    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 410:1099–1103PubMedCrossRefGoogle Scholar
  15. 15.
    Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3: 196–200PubMedCrossRefGoogle Scholar
  16. 16.
    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 - 745PubMedCrossRefGoogle Scholar
  17. 17.
    Imler JL, Hoffmann JA (2000) Signaling mechanisms in the antimicrobial host defense of Drosophila. Curr Opin Microbiol 3:16–22PubMedCrossRefGoogle Scholar
  18. 18.
    Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 3:499PubMedCrossRefGoogle Scholar
  19. 19.
    Kaisho T, Takeuchi O, Kawai T, Hoshino K, Akira S (2001) Endotoxin-induced maturation of MyD88-deficient dendritic cells. J Immunol 166: 5688–5694PubMedCrossRefGoogle Scholar
  20. 20.
    Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 18: 621–663PubMedCrossRefGoogle Scholar
  21. 21.
    Karin M, Liu Z, Zandi E (1997) AP-1 function and regulation. Curr Opin Cell Biol 9: 240–246PubMedCrossRefGoogle Scholar
  22. 22.
    Kastenbauer S, Ziegler-Heitbrock HW (1999) NF-κB 1 (p50) is upregulated in lipopolysaccharide tolerance and can block tumor necrosis factor gene expression. Infect Immun 67: 1553–1559PubMedCentralPubMedGoogle Scholar
  23. 23.
    Kawai T, Adachi O, Ogawa T, Takeda K, Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115–122PubMedCrossRefGoogle Scholar
  24. 24.
    Kobayashi K, Hernandez LD, Galan JE, Janeway CA jr, Medzhitov R, Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191 - 202PubMedCrossRefGoogle Scholar
  25. 25.
    Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374: 546–549PubMedCrossRefGoogle Scholar
  26. 26.
    Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973–983PubMedCrossRefGoogle Scholar
  27. 27.
    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: 5567–5572PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13:1015–1024PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Medzhitov R, Preston-Hurlburt P, Kopp E, Stadien A, Chen C, Ghosh S, Janeway CA jr (1998) MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2: 253–258PubMedCrossRefGoogle Scholar
  30. 30.
    Messer G, Rupec RA (2001) Nuclear factor κB (NF-κB). I. Funktion und Regulation. Hautarzt 52: 677–685PubMedCrossRefGoogle Scholar
  31. 31.
    Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, Kitamura T, Kosugi A, Kimoto M, Miyake K (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3: 667–672PubMedGoogle Scholar
  32. 32.
    Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999) The kinase TAK1 can activate the NIK-IKB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398: 252–256PubMedCrossRefGoogle Scholar
  33. 33.
    Nomura F, Akashi S, Sakao Y, Sato S, Kawai T, Matsumoto M, Nakanishi K, Kimoto M, Miyake K, Takeda K, Akira S (2000) Cutting edge: endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression. J Immunol 164: 3476–3479PubMedCrossRefGoogle Scholar
  34. 34.
    Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci U S A 97:13766–13771PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18: 6853–6866PubMedCrossRefGoogle Scholar
  36. 36.
    Poltorak A, He X, Smirnova I, Liu MY, Huffei CV, 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: 2085–2088PubMedCrossRefGoogle Scholar
  37. 37.
    Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X (2001) IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NF-κB. J Biol Chem 276: 41661–41667PubMedCrossRefGoogle Scholar
  38. 38.
    Raingeaud J, Whitmarsh AJ, Barrett T, Derijard B, Davis RJ (1996) MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Mol Cell Biol 16: 1247–1255PubMedCentralPubMedGoogle Scholar
  39. 39.
    Reis e Sousa C, Sher A, Kaye P (1999) The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr Opin Immunol 11: 392–399Google Scholar
  40. 40.
    Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R (2001) Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2: 947–950PubMedCrossRefGoogle Scholar
  41. 41.
    Schnare M, Holt AC, Takeda K, Akira S, Medzhitov R (2000) Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr Biol 10: 1139–1142PubMedCrossRefGoogle Scholar
  42. 42.
    Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J ExpMed 189: 1777–1782CrossRefGoogle Scholar
  43. 43.
    Silverman N, Maniatis T (2001) NF-κB signaling pathways in mammalian and insect innate immunity. Genes Dev 15: 2321–2342PubMedCrossRefGoogle Scholar
  44. 44.
    Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9: 271–296PubMedCrossRefGoogle Scholar
  45. 45.
    Suzuki N, Suzuki S, Duncan GS, Millar DG, Wada T, Mirtsos C, Takada H, Wakeham A, Itie A, Li S, Penninger JM, Wesche H, Ohashi PS, Mak TW, Yeh WC (2002) Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 416: 750–756PubMedCrossRefGoogle Scholar
  46. 46.
    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 13:933–940PubMedCrossRefGoogle Scholar
  47. 47.
    Treisman R (1995) Journey to the surface of the cell: Fos regulation and the SRE. EMBO J 14: 4905–4913PubMedCentralPubMedGoogle Scholar
  48. 48.
    Underhill DM, Ozinsky A (2002) Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 14: 103–110PubMedCrossRefGoogle Scholar
  49. 49.
    Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412: 346–351PubMedCrossRefGoogle Scholar
  50. 50.
    Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274:19403–19410PubMedCrossRefGoogle Scholar
  51. 51.
    Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z (1997) MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7: 837–847PubMedCrossRefGoogle Scholar
  52. 52.
    Weston CR, Davis RJ (2002) The JNK signal transduction pathway. Curr Opin Genet Dev 12:14–21PubMedCrossRefGoogle Scholar
  53. 53.
    Weston CR, Lambright DG, Davis RJ (2002) Signal transduction. MAP kinase signaling specificity. Science 296: 2345–2347PubMedCrossRefGoogle Scholar
  54. 54.
    Wright SD, Ramos RA, Tobias PS, Ulevitch RJ Mathison JC, (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249: 1431–1433PubMedCrossRefGoogle Scholar
  55. 55.
    Zhang G, Ghosh S (2002) Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem 277: 7059–7065PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Rudolf A. Rupec

There are no affiliations available

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