title: The role of transient receptor potential vanilloid 1 (TRPV1) receptors in dextran sulfate-induced colitis in mice.
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-1beta 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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 7624 Pécs, Szigeti u. 12, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Szitter
authors.forename: Gabor
authors.initials: G
authors.lastname: Pozsgai
authors.forename: Katalin
authors.initials: K
authors.lastname: Sandor
authors.forename: Krisztian
authors.initials: K
authors.lastname: Elekes
authors.forename: Agnes
authors.initials: A
authors.lastname: Kemeny
authors.forename: Aniko
authors.initials: A
authors.lastname: Perkecz
authors.forename: Janos
authors.initials: J
authors.lastname: Szolcsanyi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.forename: Erika
authors.initials: E
authors.lastname: Pinter
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D016264:Dextran Sulfate; D009195:Peroxidase
references.citation: Scand J Gastroenterol. 1995 Nov;30(11):1089-94
references.pmid: 8578169
references.citation: Am J Physiol. 1992 Feb;262(2 Pt 1):G332-7
references.pmid: 1539665
references.citation: Am J Physiol. 1997 Feb;272(2 Pt 1):G272-80
references.pmid: 9124351
references.citation: Am J Physiol. 1996 Jan;270(1 Pt 1):G79-86
references.pmid: 8772504
references.citation: Br J Pharmacol Chemother. 1968 May;33(1):32-41
references.pmid: 4298238
references.citation: Gut. 2006 Jun;55(6):815-23
references.pmid: 16299031
references.citation: J Gastroenterol. 1994 Aug;29(4):430-8
references.pmid: 7951852
references.citation: Neurogastroenterol Motil. 2007 Aug;19(8):625-9
references.pmid: 17539893
references.citation: Neurogastroenterol Motil. 2004 Dec;16(6):811-8
references.pmid: 15601431
references.citation: J Exp Med. 1995 Nov 1;182(5):1281-90
references.pmid: 7595199
references.citation: Lab Invest. 1993 Aug;69(2):238-49
references.pmid: 8350599
references.citation: Br J Pharmacol Chemother. 1967 Sep;31(1):138-51
references.pmid: 6055248
references.citation: J Clin Invest. 2007 Mar;117(3):514-21
references.pmid: 17332878
references.citation: Neuroimmunomodulation. 2008;15(1):46-53
references.pmid: 18667799
references.citation: Gut. 1992 Nov;33(11):1521-7
references.pmid: 1333439
references.citation: Pharmacol Rev. 2003 Dec;55(4):591-6
references.pmid: 14657417
references.citation: Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G621-9
references.pmid: 15764810
references.citation: Infect Immun. 2001 Apr;69(4):2277-85
references.pmid: 11254584
references.citation: J Immunol. 1995 Feb 1;154(3):1232-8
references.pmid: 7529797
references.citation: Prog Brain Res. 1996;113:343-59
references.pmid: 9009744
references.citation: Life Sci. 2001 Nov 9;69(25-26):3121-31
references.pmid: 11758837
references.citation: Inflamm Bowel Dis. 2007 Jul;13(7):918-32
references.pmid: 17343284
references.citation: Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii19-24
references.pmid: 12379615
references.citation: J Clin Invest. 1999 Mar;103(6):843-9
references.pmid: 10079105
references.citation: Pharmacol Rev. 1991 Jun;43(2):143-201
references.pmid: 1852779
references.citation: Dig Dis Sci. 1995 Mar;40(3):503-9
references.pmid: 7534678
references.citation: Regul Pept. 2007 Jun 7;141(1-3):96-104
references.pmid: 17331599
references.citation: Eur J Pharmacol. 2003 Jan 1;458(1-2):61-71
references.pmid: 12498908
references.citation: Gut. 2002 Jul;51 Suppl 1:i2-5
references.pmid: 12077054
references.citation: Nature. 1997 Oct 23;389(6653):816-24
references.pmid: 9349813
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G262-8
references.pmid: 16123200
references.citation: Microbes Infect. 2003 Feb;5(2):115-22
references.pmid: 12650769
references.citation: Lancet. 2003 Feb 1;361(9355):385-91
references.pmid: 12573376
references.citation: Dig Dis Sci. 2004 Oct;49(10):1696-704
references.pmid: 15573930
references.citation: Gastroenterology. 1990 Mar;98(3):694-702
references.pmid: 1688816
references.citation: Dig Dis Sci. 2002 Jul;47(7):1447-57
references.pmid: 12141799
references.citation: J Exp Med. 2001 Nov 5;194(9):1207-18
references.pmid: 11696587
references.citation: Digestion. 2000;62(4):240-8
references.pmid: 11070407
references.citation: Cell Tissue Res. 2002 Jan;307(1):23-33
references.pmid: 11810311
references.citation: Gastroenterology. 1994 May;106(5):1208-14
references.pmid: 7513664
references.citation: Clin Exp Immunol. 2000 Apr;120(1):46-50
references.pmid: 10759762
references.citation: J Comp Neurol. 2003 Oct 6;465(1):121-35
references.pmid: 12926020
references.citation: Neuroscience. 1998 Sep;86(2):389-98
references.pmid: 9881854
references.citation: J Clin Invest. 2003 May;111(9):1329-38
references.pmid: 12727924
references.citation: Cell Tissue Res. 2003 Mar;311(3):277-87
references.pmid: 12658436
references.citation: Neurogastroenterol Motil. 2002 Oct;14(5):459-75
references.pmid: 12358674
references.citation: Gastroenterology. 1989 Mar;96(3):795-803
references.pmid: 2914642
references.citation: Dig Dis Sci. 1993 Mar;38(3):529-37
references.pmid: 7680303
references.citation: Eur J Pharmacol. 2004 Oct 1;500(1-3):143-57
references.pmid: 15464028
references.citation: Eur J Pharmacol. 1993 Nov 9;249(2):185-90
references.pmid: 8287899
references.citation: Annu Rev Neurosci. 2001;24:487-517
references.pmid: 11283319
references.citation: Gastroenterology. 2004 Feb;126(2):520-8
references.pmid: 14762789
references.citation: Int Immunopharmacol. 2006 Sep;6(9):1404-12
references.pmid: 16846834
references.citation: J Gastrointest Surg. 2004 Nov;8(7):842-7; discussion 847-8
references.pmid: 15531237
references.citation: J Pharmacol Exp Ther. 1998 Aug;286(2):657-61
references.pmid: 9694917
references.citation: Inflamm Bowel Dis. 1997 Winter;3(4):303-13
references.pmid: 23282877
references.citation: Infect Immun. 1989 Apr;57(4):1177-85
references.pmid: 2784417
references.citation: Neurogastroenterol Motil. 2004 Dec;16(6):697-9
references.pmid: 15601418
references.citation: J Mol Med (Berl). 2006 Feb;84(2):142-6
references.pmid: 16389550
references.citation: Gut. 2007 Mar;56(3):358-64
references.pmid: 17018864
references.citation: Gastroenterology. 1988 Dec;95(6):1487-95
references.pmid: 2460392
references.citation: Gut. 2003 May;52(5):713-9
references.pmid: 12692058