TLR4 enhances histamine-mediated pruritus by potentiating TRPV1 activity

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• 作者：Hyunjung Min (1)
  Hyunkyoung Lee (1)
  Hyoungsub Lim (1)
  Yong Ho Jang (1)
  Sung Jun Chung (2)
  C Justin Lee (3)
  Sung Joong Lee (1)
  
  1. Department of Neuroscience and Physiology ; Dental Research Institute ; School of Dentistry ; Seoul National University ; Seoul ; 110-749 ; Korea
  2. Department of Physiology ; College of Medicine ; Hanyang University ; Seoul ; 133-791 ; Republic of Korea
  3. Center for Functional Connectomics ; Brain Science Institute ; Korea Institute of Science and Technology ; Seoul ; 136-791 ; Republic of Korea
  
• 关键词：Toll ; like receptor ; Itch ; Sensory neurons
• 刊名：Molecular Brain
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：1,741 KB
• 参考文献：1. Niebuhr, M, Langnickel, J, Draing, C, Renz, H, Kapp, A, Werfel, T (2008) Dysregulation of toll-like receptor-2 (TLR-2)-induced effects in monocytes from patients with atopic dermatitis: impact of the TLR-2 R753Q polymorphism. Allergy 63: pp. 728-734 CrossRef
  2. Gern, JE, Reardon, CL, Hoffjan, S, Nicolae, D, Li, Z, Roberg, KA, Neaville, WA, Carlson-Dakes, K, Adler, K, Hamilton, R, Anderson, E, Gilbertson-White, S, Tisler, C, Dasilva, D, Anklam, K, Mikus, LD, Rosenthal, LA, Ober, C, Gangnon, R, Lemanske, RF (2004) Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol Pract 113: pp. 307-314 CrossRef
  3. Konopka, L, Wierzbicki, M, Brzezinska-Blaszczyk, E (2010) Lipopolysaccharide from Porphyromonas gingivalis stimulates rat mast cells to cysteinyl leukotriene generation and upregulates Toll-like receptor 鈭? and 鈭? expression. Int J Immunopathol Pharmacol 23: pp. 803-810
  4. Varadaradjalou, S, Feger, F, Thieblemont, N, Hamouda, NB, Pleau, JM, Dy, M, Arock, M (2003) Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. Eur J Immunol 33: pp. 899-906 CrossRef
  5. Wilson, SR, Gerhold, KA, Bifolck-Fisher, A, Liu, Q, Patel, KN, Dong, X, Bautista, DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14: pp. 595-602 CrossRef
  6. Barajon, I, Serrao, G, Arnaboldi, F, Opizzi, E, Ripamonti, G, Balsari, A, Rumio, C (2009) Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem 57: pp. 1013-1023 CrossRef
  7. Liu, T, Berta, T, Xu, ZZ, Park, CK, Zhang, L, Lu, N, Liu, Q, Liu, Y, Gao, YJ, Liu, YC, Ma, Q, Dong, X, Ji, RR (2012) TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest 122: pp. 2195-2207 CrossRef
  8. Liu, T, Xu, ZZ, Park, CK, Berta, T, Ji, RR (2010) Toll-like receptor 7 mediates pruritus. Nat Neurosci 13: pp. 1460-1462 CrossRef
  9. Park, CK, Xu, ZZ, Berta, T, Han, Q, Chen, G, Liu, XJ, Ji, RR (2014) Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron 82: pp. 47-54 CrossRef
  10. Kim, SJ, Park, GH, Kim, D, Lee, J, Min, H, Wall, E, Lee, CJ, Simon, MI, Lee, SJ, Han, SK (2011) Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons. Proc Natl Acad Sci U S A 108: pp. 3371-3376 CrossRef
  11. Wadachi, R, Hargreaves, KM (2006) Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J Dent Res 85: pp. 49-53 CrossRef
  12. Bell, JK, McQueen, DS, Rees, JL (2004) Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice. Br J Pharmacol 142: pp. 374-380 CrossRef
  13. Shim, WS, Tak, MH, Lee, MH, Kim, M, Kim, M, Koo, JY, Lee, CH, Kim, M, Oh, U (2007) TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci 27: pp. 2331-2337 CrossRef
  14. Zhao, ZQ, Huo, FQ, Jeffry, J, Hampton, L, Demehri, S, Kim, S, Liu, XY, Barry, DM, Wan, L, Liu, ZC, Li, H, Turkoz, A, Ma, K, Cornelius, LA, Kopan, R, Battey, JF, Zhong, J, Chen, ZF (2013) Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest 123: pp. 4769-4780 CrossRef
  15. Lee, J, Kim, T, Hong, J, Woo, J, Min, H, Hwang, E, Lee, SJ, Lee, CJ (2012) Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels. Molecular Pain 8: pp. 2 CrossRef
  16. Diogenes, A, Ferraz, CC, Akopian, AN, Henry, MA, Hargreaves, KM (2011) LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res 90: pp. 759-764 CrossRef
  17. Ochoa-Cortes, F, Ramos-Lomas, T, Miranda-Morales, M, Spreadbury, I, Ibeakanma, C, Barajas-Lopez, C, Vanner, S (2010) Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons. Am J Physiol Gastrointest Liver Physiol 299: pp. G723-G732 CrossRef
  18. Tanga, FY, Nutile-McMenemy, N, DeLeo, JA (2005) The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A 102: pp. 5856-5861 CrossRef
  19. Fang, Z, Park, CK, Li, HY, Kim, HY, Park, SH, Jung, SJ, Kim, JS, Monteil, A, Oh, SB, Miller, RJ (2007) Molecular basis of Ca(v)2.3 calcium channels in rat nociceptive neurons. J Biol Chem 282: pp. 4757-4764 CrossRef
  20. Cho, IH, Hong, J, Suh, EC, Kim, JH, Lee, H, Lee, JE, Lee, S, Kim, CH, Kim, DW, Jo, EK, Lee, KE, Karin, M, Lee, SJ (2008) Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death. Brain 131: pp. 3019-3033 CrossRef
  21. Livak, KJ, Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(鈭扗elta Delta C(T)) Method. Methods 25: pp. 402-408 CrossRef
  
• 刊物主题：Neurosciences; Neurology;
• 出版者：BioMed Central
• ISSN：1756-6606

文摘

Background Recent studies have indicated that Toll-like receptor 4 (TLR4), a pathogen-recognition receptor that triggers inflammatory signals in innate immune cells, is also expressed on sensory neurons, implicating its putative role in sensory signal transmission. However, the possible function of sensory neuron TLR4 has not yet been formally addressed. In this regard, we investigated the role of TLR4 in itch signal transmission. Results TLR4 was expressed on a subpopulation of dorsal root ganglia (DRG) sensory neurons that express TRPV1. In TLR4-knockout mice, histamine-induced itch responses were compromised while TLR4 activation by LPS did not directly elicit an itch response. Histamine-induced intracellular calcium signals and inward currents were comparably reduced in TLR4-deficient sensory neurons. Reduced histamine sensitivity in the TLR4-deficient neurons was accompanied by a decrease in TRPV1 activity. Heterologous expression experiments in HEK293T cells indicated that TLR4 expression enhanced capsaicin-induced intracellular calcium signals and inward currents. Conclusions Our data show that TLR4 on sensory neurons enhances histamine-induced itch signal transduction by potentiating TRPV1 activity. The results suggest that TLR4 could be a novel target for the treatment of enhanced itch sensation.