The role of transient receptor potential vanilloid 1 (TRPV1) receptors in dextran sulfate-induced colitis in mice.
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.
Szitter
Istvan
I
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, 7624 Pécs, Szigeti u. 12, Hungary.
Pozsgai
Gabor
G
Sandor
Katalin
K
Elekes
Krisztian
K
Kemeny
Agnes
A
Perkecz
Aniko
A
Szolcsanyi
Janos
J
Helyes
Zsuzsanna
Z
Pinter
Erika
E
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*
D053583:Interleukin-1beta; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D016264:Dextran Sulfate; D009195:Peroxidase
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