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Journal of Molecular Neuroscience

, Volume 42, Issue 1, pp 80–88 | Cite as

The Role of Transient Receptor Potential Vanilloid 1 (Trpv1) Receptors in Dextran Sulfate-Induced Colitis in Mice

  • Istvan Szitter
  • Gabor Pozsgai
  • Katalin Sandor
  • Krisztian Elekes
  • Agnes Kemeny
  • Aniko Perkecz
  • Janos Szolcsanyi
  • Zsuzsanna Helyes
  • Erika PinterEmail author
Article

Abstract

The aim of this study was to investigate the involvement of transient receptor potential vanilloid 1 (TRPV1) receptors in oral dextran sulfate sodium-induced (DSS) colitis using TRPV1 knockout mice and their wild-type C57BL/6 counterparts. DSS (2% or 5%) was administered orally ad libitum for 7 days; the controls received tap water. Animal weight, stool consistency, and blood content were scored every day to calculate the disease activity index (DAI). After sacrificing the mice on day 7, the colons were cut into three equal segments (proximal, intermediate, and distal) for histology, myeloperoxidase (MPO), and cytokine measurements. In the 2% DSS-treated group, the lack of TRPV1 receptors decreased the DAI. Each colon segment of wild-type animals showed more than two-fold increase of MPO activity and more severe histological changes compared to the knockouts. This difference was not observed in case of 5% DSS, when extremely severe inflammation occurred in both groups. IL-1β production was not altered by the absence of TRPV1. In conclusion, activation of TRPV1 channels enhances the clinical symptoms, histopathological changes, and neutrophil accumulation induced by 2% DSS. Elucidating the modulator role of TRPV1 channels in inflammatory bowel diseases may contribute to the development of novel anti-inflammatory drugs for their therapy.

Keywords

Capsaicin-sensitive sensory nerves Disease activity index Histopathological scoring IL-1β Myeloperoxidase (MPO) activity Neurogenic inflammation 

Notes

Acknowledgments

This work was supported by grants OTKA K73044 and NK78059 of Science Please! and the Research Teams on Innovation program (SROP-4.2.2/08/1/2008-0011) grants ETT 03-380/2009 and 04-364/2009.

Z. Helyes was supported by the Janos Bolyai Postdoctoral Research Fellowship.

References

  1. Anavi-Goffer S, Coutts AA (2003) Cellular distribution of vanilloid VR1 receptor immunoreactivity in the guinea-pig myenteric plexus. Eur J Pharmacol 458:61–71CrossRefPubMedGoogle Scholar
  2. Arranz A, Abad C, Juarranz Y, Leceta J, Martinez C, Gomariz RP (2008) Vasoactive intestinal peptide as a healing mediator in Crohn's disease. Neuroimmunomodulation 15:46–53PubMedGoogle Scholar
  3. Barada KA, Kafrouni MI, CIea K (2001) Experimental colitis decreases rat jejunal amino acid absorption: role of capsaicin sensitive primary afferents. Life Sci 69(69):3121–3131CrossRefPubMedGoogle Scholar
  4. Bartho L, Benko R, Patacchini R et al (2004) Effects of capsaicin on visceral smooth muscle: a valuable tool for sensory neurotransmitter identification. Eur J Pharmacol 500(500):143–157CrossRefPubMedGoogle Scholar
  5. Boismenu R, Chen Y, Chou K, El-Sheikh A, Buelow R (2002) Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis. Ann Rheum Dis 61(Suppl 2):ii19–ii24PubMedGoogle Scholar
  6. Brun P, Mastrotto C, Beggiao E et al (2005) Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation. Am J Physiol Gastrointest Liver Physiol 288:G621–G629CrossRefPubMedGoogle Scholar
  7. Castagliuolo I, Wang CC, Valenick L, Pasha A, Nikulasson S, Carraway RE, Pothoulakis C (1999) Neurotensin is a proinflammatory neuropeptide in colonic inflammation. J Clin Investig 103:843–849CrossRefPubMedGoogle Scholar
  8. Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24(24):487–517CrossRefPubMedGoogle Scholar
  9. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(389):816–824PubMedGoogle Scholar
  10. Cavani A, Hackett CJ, Wilson KJ, Rothbard JB, Katz SI (1995) Characterization of epitopes recognized by hapten-specific CD4+ T-cells. J Immunol 154(154):1232–1238PubMedGoogle Scholar
  11. Chan CL, Facer P, JBea D (2003) Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361(361):385–391CrossRefPubMedGoogle Scholar
  12. Clapham DE, Montell C, Schultz G, Julius D (2003) Compendium of voltage-gated ion channels: transient receptor potential channels. Pharmacol Rev 55(55):591–596CrossRefPubMedGoogle Scholar
  13. Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69(69):238–249PubMedGoogle Scholar
  14. Domek MJ, Iwata F, EIea B (1995) Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in the rat. Scan J Gastroenterol 30(30):1089–1094CrossRefGoogle Scholar
  15. Egger B, Bajaj-Elliott M, MacDonald TT, Inglin R, Eysselein VE, Büchler MW (2000) Characterisation of acute murine dextran sodium sulphate colitis: cytokine profile and dose dependency. Digestion 62(62):240–248CrossRefPubMedGoogle Scholar
  16. Eliakim R, Karmeli F, Okon E, Rachmilewitz D (1995) Ketotifen ameliorates capsaicin-augmented acetic acid-induced colitis. Dig Dis Sci 40(40):503–508CrossRefPubMedGoogle Scholar
  17. Fujino K, Takami Y, de la Fuente SG, Ludwig KA, Mantyh CR (2004) Inhibition of the vanilloid receptor subtype-1 attenuates TNBS colitis. J Gastrointest Surg 8(8):842–848CrossRefPubMedGoogle Scholar
  18. Goso C, Evangelista S, Tramontana M, Manzini S, Blumberg PM, Szallasi A (1993) Topical capsaicin administration protects against trinitrobenzene sulfonic acid-induced colitis in the rat. Eur J Pharmacol 249(249):185–190CrossRefPubMedGoogle Scholar
  19. Gross KJ, Pothoulakis C (2007) Role of neuropeptides in inflammatory bowel disease. Inflamm Bowel Dis 13(13):918–932CrossRefPubMedGoogle Scholar
  20. Grundy D (2002) Neuroanatomy of visceral nociception: vagal and splanchnic afferent. Gut 1:i2–i5, Suppl 1CrossRefGoogle Scholar
  21. Helyes Z, Pinter E, Szolcsanyi J (2009) Regulatory role of sensory neuropeptides in inflammation. In: Kovacs M, Merchenthaler I (eds) Neuropeptides and peptide analogs, pp 111-141. Research SignpostGoogle Scholar
  22. Holzer P (1991) Capsaicin: cellular targets, mechanisms of action and selectivity for thin sensory neurons. Pharmacol Rev 43(43):143–201PubMedGoogle Scholar
  23. Holzer P (2002) Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain. Neurogastroenterol Motil 14(14):459–475CrossRefPubMedGoogle Scholar
  24. Holzer P (2004) Vanilloid receptor TRPV1: hot on the tongue and inflaming the colon. Neurogastroenterol Motil 16(16):697–699CrossRefPubMedGoogle Scholar
  25. Holzer P, Bartho L (1996) Sensory neurons in the intestine. In: Gepetti P, Holzer P (eds) Neurogenic inflammation. CRC Press, Boca RatonGoogle Scholar
  26. Holzer P, Maggi CA (1998) Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons. Neuroscience 86(86):389–398PubMedGoogle Scholar
  27. Iwanaga T, Hoshi O, Han H, Fujita T (1994) Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulfate sodium in the guinea pig: some possible mechanisms of cecal ulceration. J Gastroenterol 29(29):430–438CrossRefPubMedGoogle Scholar
  28. Jancso N, Jancso-Gabor A, Szolcsanyi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and treatment with capsaicin. Br J Pharmacol Chemother 31(31):138–150PubMedGoogle Scholar
  29. Jancso N, Jancso-Gabor A, Szolcsanyi J (1968) The role of the sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat. Br J Pharmacol Chemother 33(33):32–41PubMedGoogle Scholar
  30. Kazunori F, de la Fuente SG, Theodore PN, Mantyh CR (2003) Dextran sulfate sodium-induced enterocolitis is attenuated in vanilloid receptor-1 knockout mice [abstract]. Gastroenterology 124(124):300Google Scholar
  31. Kihara N, de la Fuente SG, Fujino F, Takahashi T, Pappas TN, Mantyh CR (2003) Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats. Gut 52(52):713–719CrossRefPubMedGoogle Scholar
  32. Kimball ES, Wallace NH, Schneider CR, D'Andrea MR, Homby PJ (2004) Vanilloid receptor 1 antagonist attenuate disease severity in dextran sulphate sodium-induced colitis in mice. Neurogastroenterol Motil 16(16):811–818CrossRefPubMedGoogle Scholar
  33. Krieglstein CF, Cerwinka WH, Laroux FS (2001) Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. J Exp Med 194(194):1207–1218CrossRefPubMedGoogle Scholar
  34. Leung FW (1992) Role of capsaicin-sensitive afferent nerves in mucosal injury and injury-induced hyperaemia in rat colon. Am J Physiol 262(262):G332–G337PubMedGoogle Scholar
  35. Ling K-Y, Bhalla D, Hollander D (1988) Mechanisms of carrageenan injury of IEC18 small intestinal epithelial cell monolayers. Gastroenterology 95(95):1487–1495PubMedGoogle Scholar
  36. Massa F, Sibaev A, Marsicano G, Blaudzun H, Storr M, Lutz B (2006) Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis. J Mol Med 84(84):142–146CrossRefPubMedGoogle Scholar
  37. McCafferty DM, Wallace JL, Sharkey KA (1997) Effects of chemical sympathectomy and sensory nerve ablation on experimental colitis in the rat. Am J Physiol 272(272):G272–G280PubMedGoogle Scholar
  38. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96(96):795–803PubMedGoogle Scholar
  39. Mourad FH, Barada KA, Bou Rached NA, Khoury CI, Saade NE, Nassar CF (2006) Inhibitoty effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP and nitric oxide. Am J Physiol Gastrointest Liver Physiol 290(290):G262–G268CrossRefPubMedGoogle Scholar
  40. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182(182):1281–1290CrossRefPubMedGoogle Scholar
  41. Ohkusa T, Okayasu I, Ozaki I, Yamada M, Nakaya R (1990) Changes in bacterial phagocytosis of macrophage in experimental ulcerative colitis [abstract]. Gastroenterology 98(98):A467Google Scholar
  42. Okayama M, Tsubouchi R, Kato S, Takeuchi K (2004) Protective effect of lafutidine, a novel histamine H2-receptor antagonist, on dextran sulfate sodium-induced colonic inflammation through capsaicin-sensitive afferent neurons in rats. Dig Dis Sci 49(49):1696–1704CrossRefPubMedGoogle Scholar
  43. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98(98):694–702PubMedGoogle Scholar
  44. Patterson LM, Zheng H, Ward SM, Berthoud HR (2003) Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract. Cell Tissue Res 311(311):277–287PubMedGoogle Scholar
  45. Philippe D, Chakass D, Xea T (2006) Mu opioid receptor expression is increased in inflammatory bowel diseases: implications for homeostatic intestinal inflammation. Gut 55(55):815–823CrossRefPubMedGoogle Scholar
  46. Philippe D, Dubuquoy L, Groux H, Brun V, Chuoï-mariot MTV, Gaveriaux-ruff C, J-f C, Kieffer BL, Desreumaux P (2003) Anti-inflammatory properties of the µ opioid receptor support its use in the treatment of colon inflammation. J Clin Investig 111:1329–1338PubMedGoogle Scholar
  47. Poonyachoti S, Kulkarni-Narla A, Brown DR (2002) Chemical coding of neurons expressing delta- and kappa-opioid receptor and type I vanilloid receptor immunoreactivities in the porcine ileum. Cell Tissue Res 307(307):23–33CrossRefPubMedGoogle Scholar
  48. Rachmilewitz D, Katakura K, Fea K (2004) Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 126(126):520–528CrossRefPubMedGoogle Scholar
  49. Rath HC, Schultz M, Rea F (2001) Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice. Infect Immun 69(69):2277–2285CrossRefPubMedGoogle Scholar
  50. Reinshagen M, Egger B, Procaccino F et al (1997) Neuropeptides in inflammatory bowel disease. Inflamm Bowel Dis 3(3):303–313CrossRefGoogle Scholar
  51. Reinshagen M, Flaming G, Sea E (1998) Calcitonin gene-related peptide mediates the protective effect of sensory nerves in a model of colonic injury. J Pharmacol Exp Ther 286(286):657–661PubMedGoogle Scholar
  52. Reinshagen M, Patel A, Sottili M (1994) Protective function of extrinsic sensory neurons in acute rabbit experimental colitis. Gastroenterology 106(106):1208–1214PubMedGoogle Scholar
  53. Reinshagen M, Patel A, Sottili M, French S, Stemini C, Eysselein VE (1996) Action of sensory neurons in an experimental colitis model of injury and repair. Am J Physiol 270(270):G79–G86PubMedGoogle Scholar
  54. Sartor RB, Anderle SK, Rifai N, AT GD, Cromartie WJ, Schwab JH (1989) Protracted anemia associated with chronic, relapsing systemic inflammation induced by arthropathic peptidoglycan-polysaccharide polymers in rats. Infect Immun 57(57):1177–1185PubMedGoogle Scholar
  55. Setoyama H, Imaoka A, Ishikawa H, Umesaki Y (2003) Prevention of gut inflammation by Bifidobacterium in dextran sulfate-treated gnotobiotic mice associated with Bacteroides strains isolated from ulcerative colitis patients. Microbes Infect 5(5):115–122CrossRefPubMedGoogle Scholar
  56. Storr M (2007) TRPV1 in colitis: is it a good or a bad receptor?—a viewpoint. Neurogastroenterol Motil 19(19):625–629CrossRefPubMedGoogle Scholar
  57. Strober W, Fuss I, Mannon P (2007) The fundamental basis of inflammatory bowel disease. J Clin Invest 117(117):514–521CrossRefPubMedGoogle Scholar
  58. Szolcsanyi J (1982) Capsaicin type pungent agents producing pyrexia. In: Milton AS (ed) Handbook of experimental pharmacology. Springer, BerlinGoogle Scholar
  59. Szolcsanyi J (1984) Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function. In: Chahl LA, Szolcsanyi J, Lembeck F (eds) Antidromic vasodilatation and neurogenic inflammation. Akadémiai Kiadó, Budapest, pp 27–56Google Scholar
  60. Szolcsanyi J (1996) Capsaicin-sensitive sensory nerve terminals with local systemic efferent functions: facts and scopes of an unorthodox neuroregulatory mechanism. Prog Brain Res 113(113):343–359CrossRefPubMedGoogle Scholar
  61. Talero E, Sánchez-Fidalgo S, Ramón Calvo J, Motilva V (2006) Galanin in the trinitrobenzene sulfonic acid rat model of experimental colitis. Int Immunopharmacol 6:1404–1412CrossRefPubMedGoogle Scholar
  62. Talero E, Sanchez-Fidalgo S, Calvo JR, Motilva V (2007) Chronic administration of galanin attenuates the TNBS-induced colitis in rats. Regul Pept 141(141):96–104CrossRefPubMedGoogle Scholar
  63. Tamaru T, Kobayashi H, Kishimoto S, Kajiyama G, Shimamoto F, Brown WR (1993) Histochemical study of colonic cancer in experimental colitis of rats. Dig Dis Sci 38(38):529–537CrossRefPubMedGoogle Scholar
  64. Verdu EF, Bercik P, Bea C (2000) Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice. Clin Exp Immunol 120(120):46–50CrossRefPubMedGoogle Scholar
  65. Verma-Gondhu MF, Verdu E, Bercik P, Blennerhassett AP, Al-Mutawaly N, Ghia J-E, Collins MS (2007) Visceral pain perception is determined by the duration of colitis and associated neuropeptide expression in the mouse. Gut 56:358–364CrossRefGoogle Scholar
  66. Vetuschi A, Latella G, Sferra R, Caprilli R, Gaudio E (2002) Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats. Dig Dis Sci 47(47):1447–1457CrossRefPubMedGoogle Scholar
  67. Ward SM, Bayguinov J, Won KJ, Grundy D, Berthoud HR (2003) Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract. J Comp Neurol 465(465):121–135CrossRefPubMedGoogle Scholar
  68. Yamada M, Ohkusa T, Okayasu I (1992) Occurence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium. Gut 33(33):1521–1527CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Istvan Szitter
    • 1
  • Gabor Pozsgai
    • 1
  • Katalin Sandor
    • 1
  • Krisztian Elekes
    • 1
  • Agnes Kemeny
    • 1
  • Aniko Perkecz
    • 1
  • Janos Szolcsanyi
    • 1
  • Zsuzsanna Helyes
    • 1
  • Erika Pinter
    • 1
    Email author
  1. 1.Department of Pharmacology and Pharmacotherapy, Faculty of MedicineUniversity of PécsPécs, Szigeti u. 12Hungary

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