Skip to main content
SpringerLink
Log in

Neuroinflammation and Toll-Like Receptors in the Skin

  • Chapter
Book cover Neuroimmunology of the Skin

  • 1182 Accesses

  • Toll-like receptors are key facilitators of innate immunity within the skin.

  • Different TLRs are activated by various exogenous and endogenous ligands.

  • TLR signaling provides a mechanism of activating rapid and directed immune responses in defense of the host.

  • Evidence for TLR expression and function has recently been discovered in skin and neuronal tissues.

  • The nervous system and specific neuromediators play a role in activation and subsequent response of the TLRs.

  • Directed therapy that modifies TLR signaling may provide new avenues of treating auto-immune disease, skin cancer, and conditions of inappropriate inflammation.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abreu MT, et al (2001) Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol 167(3): 1609–1616

    PubMed  CAS  Google Scholar 

  2. Adachi O, et al (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9(1): 143–150

    Article  PubMed  CAS  Google Scholar 

  3. Akira S (2003) Toll-like receptor signaling. J Biol Chem 278(40):38105–38108

    Article  PubMed  CAS  Google Scholar 

  4. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4(7):499–511

    Article  PubMed  CAS  Google Scholar 

  5. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2(8):675–680

    Article  PubMed  CAS  Google Scholar 

  6. Akira S, Yamamoto M, Takeda K (2003) Role of adapters in Toll-like receptor signalling. Biochem Soc Trans 31(Pt 3):637–642

    Article  PubMed  CAS  Google Scholar 

  7. Albertin G, et al (2003) Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis. Int J Mol Med 11(5):635–639

    PubMed  CAS  Google Scholar 

  8. Alexopoulou L, et al (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732–738

    Article  PubMed  CAS  Google Scholar 

  9. Aliprantis AO, et al (1999) Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 285(5428):736–739

    Article  PubMed  CAS  Google Scholar 

  10. Aliprantis AO, et al (2000) The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J 19(13): 3325–3336

    Article  PubMed  CAS  Google Scholar 

  11. Ansel JC, et al (1993) Substance P selectively activates TNF-alpha gene expression in murine mast cells. J Immunol 150(10):4478–4485

    PubMed  CAS  Google Scholar 

  12. Ansel JC, et al (1997) Interactions of the skin and nervous system. J Investig Dermatol Symp Proc 2(1):23–26

    PubMed  CAS  Google Scholar 

  13. Arany I, et al (1996) Regulation of inducible nitric oxide synthase mRNA levels by differentiation and cytokines in human keratinocytes. Biochem Biophys Res Commun 220(3):618–622

    Article  PubMed  CAS  Google Scholar 

  14. Armant MA, Fenton MJ (2002) Toll-like receptors: a family of pattern-recognition receptors in mammals. Genome Biol 3(8):REVIEWS3011

    Google Scholar 

  15. Baker BS, et al (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148(4):670–679

    Article  PubMed  CAS  Google Scholar 

  16. Basu S, Fenton MJ (2004) Toll-like receptors: function and roles in lung disease. Am J Physiol Lung Cell Mol Physiol 286(5):L887–L892

    Article  PubMed  CAS  Google Scholar 

  17. Bauer S, et al (2001) Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA 98(16):9237–9242

    Article  PubMed  CAS  Google Scholar 

  18. Bosisio D, et al (2002) Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 99(9):3427–3431

    Article  PubMed  CAS  Google Scholar 

  19. Bowie A, et al (2000) A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc Natl Acad Sci USA 97(18): 10162–10167

    Article  PubMed  CAS  Google Scholar 

  20. Brain SD, Moore PK (1999) Pain and neurogenic inflammation. In: Parnham MJ (ed) Progress in Inflammation Research, Birkhauser, Basel

    Google Scholar 

  21. Breiman A, et al (2005) Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J Virol 79(7):3969–3978

    Article  PubMed  CAS  Google Scholar 

  22. Bsibsi M, et al (2002) Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol 61(11): 1013–1021

    PubMed  CAS  Google Scholar 

  23. Burns K, et al (2003) Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J Exp Med 197(2):263–268

    Article  PubMed  Google Scholar 

  24. Carty M, et al (2006) The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol 7(10): 1074–1081

    Article  PubMed  CAS  Google Scholar 

  25. Chen H, et al (2006) Modulation of Toll-like receptor expression in murine and human keratinocytes by substance P: another link between the seurosensory and innate immune systems in the skin. J Invest Dermatol 127:124

    Google Scholar 

  26. Choi KC, et al (2006) Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1. Nat Immunol 7(10):1057–1065

    Article  PubMed  CAS  Google Scholar 

  27. Diebold SS, et al (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303(5663): 1529–1531

    Article  PubMed  CAS  Google Scholar 

  28. DiPerna G, et al (2004) Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. J Biol Chem 279(35):36570–36578

    Article  PubMed  CAS  Google Scholar 

  29. Farina C, et al (2005) Preferential expression and function of Toll-like receptor 3 in human astrocytes. J Neuroimmunol 159(1–2):12–19

    Article  PubMed  CAS  Google Scholar 

  30. Faure E, et al (2000) Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem 275(15):11058–11063

    Article  PubMed  CAS  Google Scholar 

  31. Frohm M, et al (1997) The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem 272(24):15258–15263

    Article  PubMed  CAS  Google Scholar 

  32. Gewirtz AT, et al (2001) Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167(4): 1882–1885

    PubMed  CAS  Google Scholar 

  33. Gibson SJ, et al (2002) Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell Immunol 218(1–2):74–86

    Article  PubMed  CAS  Google Scholar 

  34. Gomariz RP, et al (2005) Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP. J Leukoc Biol 78(2):491–502

    Article  PubMed  CAS  Google Scholar 

  35. Grando SA (1997) Biological functions of keratinocyte cholinergic receptors. J Investig Dermatol Symp Proc 2(1):41–48

    PubMed  CAS  Google Scholar 

  36. Grando SA, et al (1993) Human keratinocytes synthesize, secrete, and degrade acetylcholine. J Invest Dermatol 101(1):32–36

    Article  PubMed  CAS  Google Scholar 

  37. Gutierrez-Canas I, et al (2006) VIP down-regulates TLR4 expression and TLR4-mediated chemokine production in human rheumatoid synovial fibroblasts. Rheumatology (Oxford) 45(5):527–532

    Article  CAS  Google Scholar 

  38. Haga IR, Bowie AG (2005) Evasion of innate immunity by vaccinia virus. Parasitology 130(Suppl):S11–S25

    Article  PubMed  CAS  Google Scholar 

  39. Harder J, et al (1997) A peptide antibiotic from human skin. Nature 387(6636):861

    Article  PubMed  CAS  Google Scholar 

  40. Harder J, et al (2001) Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276(8):5707–5713

    Article  PubMed  CAS  Google Scholar 

  41. Harzenetter MD, et al (2007) Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER. J Immunol 179(1):607–615

    PubMed  CAS  Google Scholar 

  42. Hasan U, et al (2005) Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 174(5):2942–2950

    PubMed  CAS  Google Scholar 

  43. 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(2):269–279

    Article  PubMed  CAS  Google Scholar 

  44. Hayashi F, et al (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832):1099–1103

    Article  PubMed  CAS  Google Scholar 

  45. Heesemann J, Sing A, Trulzsch K (2006) Yersinia’s stratagem: targeting innate and adaptive immune defense. Curr Opin Microbiol 9(1):55–61

    Article  PubMed  CAS  Google Scholar 

  46. Heil F, et al (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303(5663):1526–1529

    Article  PubMed  CAS  Google Scholar 

  47. Hemmi H, et al (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3(2):196–200

    Article  PubMed  CAS  Google Scholar 

  48. Hertz CJ, et al (2001) Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J Immunol 166(4):2444–2450

    PubMed  CAS  Google Scholar 

  49. Hirschfeld M, et al (2001) Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun 69(3): 1477–1482

    Article  PubMed  CAS  Google Scholar 

  50. Hoffmann JA, et al (1999) Phylogenetic perspectives in innate immunity. Science 284(5418):1313–1318

    Article  PubMed  CAS  Google Scholar 

  51. Hornef MW, et al (2002) Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 195(5):559–570

    Article  PubMed  CAS  Google Scholar 

  52. Horng T, Barton GM, Medzhitov R (2001) TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol 2(9):835–841

    Article  PubMed  CAS  Google Scholar 

  53. Hosoi J, et al (1993) Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature 363(6425):159–163

    Article  PubMed  CAS  Google Scholar 

  54. Inohara N, Nunez G (2001) The NOD: a signaling module that regulates apoptosis and host defense against pathogens. Oncogene 20(44):6473–6481

    Article  PubMed  CAS  Google Scholar 

  55. Ito T, et al (2002) Interferon-alpha and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets. J Exp Med 195(11):1507–1512

    Article  PubMed  CAS  Google Scholar 

  56. Iwami KI, et al (2000) Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 165(12):6682–6686

    PubMed  CAS  Google Scholar 

  57. Jackson AC, Rossiter JP, Lafon M (2006) Expression of Toll-like receptor 3 in the human cerebellar cortex in rabies, herpes simplex encephalitis, and other neurological diseases. J Neurovirol 12(3):229–234

    Article  PubMed  CAS  Google Scholar 

  58. Janeway CA, Jr., Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216

    Article  PubMed  CAS  Google Scholar 

  59. Jarrossay D, et al (2001) Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 31(11):3388–3393

    Article  PubMed  CAS  Google Scholar 

  60. Kadowaki N, et al (2001) Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 194(6):863–869

    Article  PubMed  CAS  Google Scholar 

  61. Kaisho T, Akira S (2002) Toll-like receptors as adjuvant receptors. Biochim Biophys Acta 1589(1):1–13

    Article  PubMed  CAS  Google Scholar 

  62. Kawai K, et al (2002) Expression of functional Toll-like receptor 2 on human epidermal keratinocytes. J Dermatol Sci 30(3): 185–194

    Article  PubMed  CAS  Google Scholar 

  63. Kelly D, Conway S, Bacterial modulation of mucosal innate immunity. Mol Immunol 42(8):895–901

    Google Scholar 

  64. Kim J, et al (2002) Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 169(3):1535–1541

    PubMed  CAS  Google Scholar 

  65. Klinman DM, et al (2004) Use of CpG oligodeoxynucleotides as immune adjuvants. Immunol Rev 199:201–216

    Article  PubMed  CAS  Google Scholar 

  66. Kobayashi K, et al (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110(2): 191–202

    Article  PubMed  CAS  Google Scholar 

  67. Kodali S, et al (2004) Vasoactive intestinal peptide modulates Langerhans cell immune function. J Immunol 173(10):6082–6088

    PubMed  CAS  Google Scholar 

  68. Koedel U, et al (2004) MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS. Brain 127(Pt 6):1437–1445

    Article  PubMed  Google Scholar 

  69. Kopp E, Medzhitov R (2003) Recognition of microbial infection by Toll-like receptors. Curr Opin Immunol 15(4):396–401

    Article  PubMed  CAS  Google Scholar 

  70. Krieg AM (2000) The role of CpG motifs in innate immunity. Curr Opin Immunol 12(1):35–43

    Article  PubMed  CAS  Google Scholar 

  71. Krug A, et al (2001) Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur J Immunol 31(10):3026–3037

    Article  PubMed  CAS  Google Scholar 

  72. Lafon M, et al (2006) The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J Mol Neurosci 29(3):185–194

    Article  PubMed  CAS  Google Scholar 

  73. Lambrecht BN (2001) Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation. Respir Res 2(3):133–138

    Article  PubMed  CAS  Google Scholar 

  74. LeBouder E, et al (2003) Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol 171(12):6680–6689

    PubMed  CAS  Google Scholar 

  75. Lebre MC, et al (2003) Double-stranded RNA-exposed human keratinocytes promote Thl responses by inducing a Type-1 polarized phenotype in dendritic cells: role of keratinocyte-derived tumor necrosis factor alpha, type I interferons, and interleukin-18. J Invest Dermatol 120(6):990–997

    Article  PubMed  CAS  Google Scholar 

  76. Li K, et al (2005) Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIf. Proc Natl Acad Sci USA 102(8):2992–2997

    Article  PubMed  CAS  Google Scholar 

  77. Liew FY, et al (2005) Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol 5(6):446–458

    Article  PubMed  CAS  Google Scholar 

  78. Lin Y, et al (2000) The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 275(32):24255–24263

    Article  PubMed  CAS  Google Scholar 

  79. Lu Y, et al (2007) Alpha-melanocyte-stimulating hormone inhibits the expression and function of keratinocyte TLR-2. J Invest Dermatol 127:S133

    Google Scholar 

  80. Lund JM, et al (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 101(15):5598–5603

    Article  PubMed  CAS  Google Scholar 

  81. Mackenzie-Wood A, et al (2001) Imiquimod 5% cream in the treatment of Bowen’s disease. J Am Acad Dermatol 44(3):462–470

    Article  PubMed  CAS  Google Scholar 

  82. Marriott I, Bost KL (2001) Expression of authentic substance P receptors in murine and human dendritic cells. J Neuroimmunol 114(1–2):131–141

    Article  PubMed  CAS  Google Scholar 

  83. Matsuguchi T, et al (2000) Gene expressions of Toll-like receptor 2, but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages. J Immunol 165(10):5767–5772

    PubMed  CAS  Google Scholar 

  84. McCurdy JD, Lin TJ, Marshall JS (2001) Toll-like receptor 4-mediated activation of murine mast cells. J Leukoc Biol 70(6):977–984

    PubMed  CAS  Google Scholar 

  85. McInturff JE, Modlin RL, Kim J (2005) The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. J Invest Dermatol 125(1):1–8

    Article  PubMed  CAS  Google Scholar 

  86. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135–145

    Article  PubMed  CAS  Google Scholar 

  87. Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388(6640):394–397

    Article  PubMed  CAS  Google Scholar 

  88. Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106(3):255–258

    Article  PubMed  CAS  Google Scholar 

  89. Melroe GT, DeLuca NA, Knipe DM (2004) Herpes simplex virus 1 has multiple mechanisms for blocking virus-induced interferon production. J Virol 78(16):8411–8420

    Article  PubMed  CAS  Google Scholar 

  90. Mempel M, et al (2003) Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent. J Invest Dermatol 121(6):1389–1396

    Article  PubMed  CAS  Google Scholar 

  91. Mibayashi M, et al (2007) Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol 81(2):514–524

    Article  PubMed  CAS  Google Scholar 

  92. Michelsen KS, et al (2001) The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCS). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. J Biol Chem 276(28):25680–15686

    Article  PubMed  CAS  Google Scholar 

  93. Miettinen M, et al (2001) IFNs activate toll-like receptor gene expression in viral infections. Genes Immun 2(6):349–355

    Article  PubMed  CAS  Google Scholar 

  94. Milner P, et al (2004) Regulation of substance P mRNA expression in human dermal microvascular endothelial cells. Clin Exp Rheumatol 22(3 Suppl 33):S24–S27

    PubMed  CAS  Google Scholar 

  95. Muzio M, et al (2000) Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 164(11):5998–6004

    PubMed  CAS  Google Scholar 

  96. Naik S, et al (2001) Absence ofToll-like receptor4 explains endotoxin hyporesponsiveness in human intestinal epithelium. J Pediatr Gastroenterol Nutr 32(4):449–453

    Article  PubMed  CAS  Google Scholar 

  97. O’Neill LA (2003) The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochem Soc Trans 31(Pt 3):643–647

    Article  PubMed  CAS  Google Scholar 

  98. Oliveira RB, et al (2003) Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71(3):1427–1433

    Article  PubMed  CAS  Google Scholar 

  99. Pai RK, et al (2003) Inhibition of IFN-gamma-induced class II transactivator expression by a 19-kDa lipoprotein from Mycobacterium tuberculosis: a potential mechanism for immune evasion. J Immunol 171(1):175–184

    PubMed  CAS  Google Scholar 

  100. Peters EM, et al (2006) Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance. J Invest Dermatol 126(9):1937–1947

    Article  PubMed  CAS  Google Scholar 

  101. Pivarcsi A, et al (2003) Expression and function of Toll-like receptors 2 and4 in human keratinocytes. Int Immunol 15(6):721–730

    Article  PubMed  CAS  Google Scholar 

  102. Prehaud C, et al (2005) Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J Virol 79(20):12893–12904

    Article  PubMed  CAS  Google Scholar 

  103. Prinz M, et al (2006) Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J Clin Invest 116(2):456–464

    Article  PubMed  CAS  Google Scholar 

  104. Rakoff-Nahoum S, et al (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118(2):229–241

    Article  PubMed  CAS  Google Scholar 

  105. Roosterman D, et al (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86(4):1309–1379

    Article  PubMed  CAS  Google Scholar 

  106. Schallreuter KU (1997) Epidermal adrenergic signal transduction as part of the neuronal network in the human epidermis. J Investig Dermatol Symp Proc 2(1):37–40

    PubMed  CAS  Google Scholar 

  107. Schmidt R, et al (1995) Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci 15(1 Pt 1):333–341

    PubMed  CAS  Google Scholar 

  108. Scholzen T, et al (1998) Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol 7(2–3):81–96

    Article  PubMed  CAS  Google Scholar 

  109. Scholzen TE, et al (1999) Expression of proopiomelanocortin peptides and prohormone convertases by human dermal microvascular endothelial cells. Ann NY Acad Sci 885:444–447

    Article  PubMed  CAS  Google Scholar 

  110. Shuto T, et al (2001) Activation of NF-kappa B by non-typeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha /beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc Natl Acad Sci USA 98(15):8774–8779

    Article  PubMed  CAS  Google Scholar 

  111. Shuto T, et al (2002) Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor2 expression via a negative cross-talk with p38 MAP kinase. J Biol Chem 277(19):17263–17270

    Article  PubMed  CAS  Google Scholar 

  112. Smiley ST, King JA, Hancock WW (2001) Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 167(5):2887–2894

    PubMed  CAS  Google Scholar 

  113. Smith MF, Jr., et al (2003) Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 278(35):32552–32560

    Article  PubMed  CAS  Google Scholar 

  114. Song IS, et al (1998) CD14 expression in rabbit and human corneas. Invest Ophthalmol Vis Sci 39:S773

    Google Scholar 

  115. Song IS, et al (1999) The expression and function of the LPS, CD14/Toll-like receptor 2 (TLR2) complex in human cornea. Invest Ophthalmol Vis Sci 40:S794

    Google Scholar 

  116. Song IS, et al (1999) The identity and function of CD14 LPS receptor and toll-like receptor 2 in a human epithelial cell line. J Invest Dermatol 112:546

    Google Scholar 

  117. Song PI, et al (2001) The expression of functional LPS receptor proteins CD14 and toll-like receptor 4 in human corneal cells. Invest Ophthalmol Vis Sci 42(12):2867–2877

    PubMed  CAS  Google Scholar 

  118. Song PI, et al (2002) Human keratinocytes express functional CD14 and toll-like receptor 4. J Invest Dermatol 119(2):424–432

    Article  PubMed  CAS  Google Scholar 

  119. Song PI, et al (2002) Lipoteichoic acid-induced keratinocyte activation is mediated by Toll-like receptor 4. J Invest Dermatol 119:300

    Article  Google Scholar 

  120. Song PI, et al (2003) The expression of Toll-like receptors, MD-2 and CD14 in mouse keratinocytes. J Invest Dermatol 121:Abstract 0945

    Google Scholar 

  121. Stack J, et al (2005) Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. J Exp Med 201(6):1007–1018

    Article  PubMed  CAS  Google Scholar 

  122. Steinhoff M, et al (2003) Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol 139(11):1479–1488

    Article  PubMed  Google Scholar 

  123. Steinhoff M, et al (2006) Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol 126(8):1705–1718

    Article  PubMed  CAS  Google Scholar 

  124. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5(6):575–581

    Article  PubMed  CAS  Google Scholar 

  125. Summers AE, Whelan CJ, Parsons ME (2003) Nicotinic acetylcholine receptor subunits and receptor activity in the epithelial cell line HT29. Life Sci 72(18–19):2091–2094

    Article  PubMed  CAS  Google Scholar 

  126. Supajatura V, et al (2002) Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J Clin Invest 109(10):1351–1359

    PubMed  CAS  Google Scholar 

  127. Tahara K, et al (2006) Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 129(Pt 11):3006–3019

    Article  PubMed  Google Scholar 

  128. Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376

    Article  PubMed  CAS  Google Scholar 

  129. Tlaskalova-Hogenova, H, et al (2004) Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 93(2–3):97–108

    Article  PubMed  CAS  Google Scholar 

  130. Tsuji S, et al (2000) Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin: involvement of toll-like receptors. Infect Immun 68(12):6883–6890

    Article  PubMed  CAS  Google Scholar 

  131. Vabulas RM, et al (2002) HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 277(17):15107–15112

    Article  PubMed  CAS  Google Scholar 

  132. Vetrugno R, et al (2003) Sympathetic skin response: basic mechanisms and clinical applications. Clin Auton Res 13(4):256–270

    Article  PubMed  Google Scholar 

  133. Wadachi R, Hargreaves KM (2006) Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J Dent Res 85(1):49–53

    Article  PubMed  CAS  Google Scholar 

  134. Wang T, Lafuse WP, Zwilling BS (2000) Regulation of toll-like receptor 2 expression by macrophages following Mycobacterium avium infection. J Immunol 165(11):6308–6313

    PubMed  CAS  Google Scholar 

  135. Weller R (2003) Nitric oxide: a key mediator in cutaneous physiology. Clin Exp Dermatol 28(5):511–514

    Article  PubMed  CAS  Google Scholar 

  136. Yamamoto M, et al (2002) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420(6913):324–329

    Article  PubMed  CAS  Google Scholar 

  137. Yamamoto M, et al (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301(5633):640–643

    Article  PubMed  CAS  Google Scholar 

  138. Yamamoto M, et al (2003) TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 4(11):1144–1150

    Article  PubMed  CAS  Google Scholar 

  139. Yamamoto S, et al (1992) Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity. J Immunol 148(12):4072–4076

    PubMed  CAS  Google Scholar 

  140. Zhang D, et al (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303(5663):1522–1526

    Article  PubMed  CAS  Google Scholar 

  141. Zhang G, Ghosh S (2002) Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem 277(9):7059–7065

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA

    B. Rothschild, Y. Lu, H. Chen, P. I. Song, C. A. Armstrong & J. C. Ansel

Authors
  1. B. Rothschild
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. I. Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. A. Armstrong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. C. Ansel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Rothschild .

Editor information

Editors and Affiliations

  1. Weill Cornell Medical College Department of Dermatology, Cornell University, 1300 York Ave., 10021, New York, NY, USA

    Richard D. Granstein MD

  2. Medizinische Einrichtungen Klinik und Poliklinik für, Universitätsklinikum Münster, Von-Esmarch-Str. 56, 48149, Münster, Germany

    Thomas A. Luger MD

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Rothschild, B., Lu, Y., Chen, H., Song, P.I., Armstrong, C.A., Ansel, J.C. (2009). Neuroinflammation and Toll-Like Receptors in the Skin. In: Granstein, R.D., Luger, T.A. (eds) Neuroimmunology of the Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-35989-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-35989-0_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-35986-9

  • Online ISBN: 978-3-540-35989-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation