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

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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.

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References

  • Anavi-Goffer S, Coutts AA (2003) Cellular distribution of vanilloid VR1 receptor immunoreactivity in the guinea-pig myenteric plexus. Eur J Pharmacol 458:61–71

    Article  CAS  PubMed  Google Scholar 

  • 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 15:46–53

    CAS  PubMed  Google Scholar 

  • 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):3121–3131

    Article  CAS  PubMed  Google Scholar 

  • 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):143–157

    Article  CAS  PubMed  Google Scholar 

  • 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–ii24

    CAS  PubMed  Google Scholar 

  • 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–G629

    Article  CAS  PubMed  Google Scholar 

  • 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 103:843–849

    Article  CAS  PubMed  Google Scholar 

  • Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24(24):487–517

    Article  CAS  PubMed  Google Scholar 

  • 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):816–824

    CAS  PubMed  Google Scholar 

  • 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):1232–1238

    CAS  PubMed  Google Scholar 

  • Chan CL, Facer P, JBea D (2003) Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361(361):385–391

    Article  CAS  PubMed  Google Scholar 

  • Clapham DE, Montell C, Schultz G, Julius D (2003) Compendium of voltage-gated ion channels: transient receptor potential channels. Pharmacol Rev 55(55):591–596

    Article  PubMed  Google Scholar 

  • Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69(69):238–249

    CAS  PubMed  Google Scholar 

  • 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):1089–1094

    Article  CAS  Google Scholar 

  • 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):240–248

    Article  CAS  PubMed  Google Scholar 

  • Eliakim R, Karmeli F, Okon E, Rachmilewitz D (1995) Ketotifen ameliorates capsaicin-augmented acetic acid-induced colitis. Dig Dis Sci 40(40):503–508

    Article  CAS  PubMed  Google Scholar 

  • 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):842–848

    Article  PubMed  Google Scholar 

  • 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):185–190

    Article  CAS  PubMed  Google Scholar 

  • Gross KJ, Pothoulakis C (2007) Role of neuropeptides in inflammatory bowel disease. Inflamm Bowel Dis 13(13):918–932

    Article  PubMed  Google Scholar 

  • Grundy D (2002) Neuroanatomy of visceral nociception: vagal and splanchnic afferent. Gut 1:i2–i5, Suppl 1

    Article  Google Scholar 

  • 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 Signpost

  • Holzer P (1991) Capsaicin: cellular targets, mechanisms of action and selectivity for thin sensory neurons. Pharmacol Rev 43(43):143–201

    CAS  PubMed  Google Scholar 

  • Holzer P (2002) Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain. Neurogastroenterol Motil 14(14):459–475

    Article  CAS  PubMed  Google Scholar 

  • Holzer P (2004) Vanilloid receptor TRPV1: hot on the tongue and inflaming the colon. Neurogastroenterol Motil 16(16):697–699

    Article  PubMed  Google Scholar 

  • Holzer P, Bartho L (1996) Sensory neurons in the intestine. In: Gepetti P, Holzer P (eds) Neurogenic inflammation. CRC Press, Boca Raton

    Google Scholar 

  • Holzer P, Maggi CA (1998) Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons. Neuroscience 86(86):389–398

    CAS  PubMed  Google Scholar 

  • 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):430–438

    Article  CAS  PubMed  Google Scholar 

  • 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):138–150

    CAS  PubMed  Google Scholar 

  • 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):32–41

    CAS  PubMed  Google Scholar 

  • 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):300

    Google Scholar 

  • 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):713–719

    Article  CAS  PubMed  Google Scholar 

  • 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):811–818

    Article  CAS  PubMed  Google Scholar 

  • 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):1207–1218

    Article  CAS  PubMed  Google Scholar 

  • 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–G337

    CAS  PubMed  Google Scholar 

  • Ling K-Y, Bhalla D, Hollander D (1988) Mechanisms of carrageenan injury of IEC18 small intestinal epithelial cell monolayers. Gastroenterology 95(95):1487–1495

    CAS  PubMed  Google Scholar 

  • 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):142–146

    Article  CAS  PubMed  Google Scholar 

  • 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–G280

    CAS  PubMed  Google Scholar 

  • 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):795–803

    CAS  PubMed  Google Scholar 

  • 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–G268

    Article  CAS  PubMed  Google Scholar 

  • 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):1281–1290

    Article  CAS  PubMed  Google Scholar 

  • 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):A467

    Google Scholar 

  • 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):1696–1704

    Article  CAS  PubMed  Google Scholar 

  • 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):694–702

    CAS  PubMed  Google Scholar 

  • 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):277–287

    CAS  PubMed  Google Scholar 

  • 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):815–823

    Article  CAS  PubMed  Google Scholar 

  • 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 111:1329–1338

    CAS  PubMed  Google Scholar 

  • 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):23–33

    Article  CAS  PubMed  Google Scholar 

  • 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):520–528

    Article  CAS  PubMed  Google Scholar 

  • 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):2277–2285

    Article  CAS  PubMed  Google Scholar 

  • Reinshagen M, Egger B, Procaccino F et al (1997) Neuropeptides in inflammatory bowel disease. Inflamm Bowel Dis 3(3):303–313

    Article  Google Scholar 

  • 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):657–661

    CAS  PubMed  Google Scholar 

  • Reinshagen M, Patel A, Sottili M (1994) Protective function of extrinsic sensory neurons in acute rabbit experimental colitis. Gastroenterology 106(106):1208–1214

    CAS  PubMed  Google Scholar 

  • 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–G86

    CAS  PubMed  Google Scholar 

  • 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):1177–1185

    CAS  PubMed  Google Scholar 

  • 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):115–122

    Article  PubMed  Google Scholar 

  • Storr M (2007) TRPV1 in colitis: is it a good or a bad receptor?—a viewpoint. Neurogastroenterol Motil 19(19):625–629

    Article  CAS  PubMed  Google Scholar 

  • Strober W, Fuss I, Mannon P (2007) The fundamental basis of inflammatory bowel disease. J Clin Invest 117(117):514–521

    Article  CAS  PubMed  Google Scholar 

  • Szolcsanyi J (1982) Capsaicin type pungent agents producing pyrexia. In: Milton AS (ed) Handbook of experimental pharmacology. Springer, Berlin

    Google Scholar 

  • 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 27–56

    Google Scholar 

  • 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):343–359

    Article  CAS  PubMed  Google Scholar 

  • Talero E, Sánchez-Fidalgo S, Ramón Calvo J, Motilva V (2006) Galanin in the trinitrobenzene sulfonic acid rat model of experimental colitis. Int Immunopharmacol 6:1404–1412

    Article  CAS  PubMed  Google Scholar 

  • 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):96–104

    Article  CAS  PubMed  Google Scholar 

  • 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):529–537

    Article  CAS  PubMed  Google Scholar 

  • 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):46–50

    Article  CAS  PubMed  Google Scholar 

  • 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 56:358–364

    Article  Google Scholar 

  • 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):1447–1457

    Article  PubMed  Google Scholar 

  • 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):121–135

    Article  PubMed  Google Scholar 

  • 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):1521–1527

    Article  CAS  PubMed  Google Scholar 

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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.

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Correspondence to Erika Pinter.

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E. Pinter and Z. Helyes made equal contributions to the present work. Similarly, I. Szitter and G. Pozsgai contributed equally to this paper.

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Szitter, I., Pozsgai, G., Sandor, K. et al. The Role of Transient Receptor Potential Vanilloid 1 (Trpv1) Receptors in Dextran Sulfate-Induced Colitis in Mice. J Mol Neurosci 42, 80–88 (2010). https://doi.org/10.1007/s12031-010-9366-5

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