Endothelin in human inflammatory bowel disease: comparison to rat trinitrobenzenesulphonic acid-induced colitis.
There have been suggestions that endothelins (ET-1, ET-2, ET-3) are involved in the pathogenesis of human inflammatory bowel disease (IBD). Furthermore, the non-selective endothelin receptor antagonist, bosentan, ameliorates colonic inflammation in TNBS colitis in rats. However, no studies have measured the tissue expression and release of endothelins in human IBD in direct comparison to experimental TNBS colitis. Mucosal biopsies were obtained from 114 patients (42 Crohn's colitis, 35 ulcerative colitis and 37 normal) and compared to whole colonic segments from rats with TNBS colitis. ET-1/2 levels were reduced in human IBD but greatly increased in experimental TNBS colitis. RT-PCR indicated ET-2 was the predominant endothelin isoform in human IBD whereas ET-1 prevailed in the TNBS model. No associations were found between human IBD and tissue expression, content or release of ET-1/2. Our study shows, therefore, that unlike TNBS colitis in rats, in which ET-1/2 levels are greatly elevated and ET receptor antagonists are efficacious, there is no significant link between endothelins and human IBD.
McCartney
Sara A
SA
Digestive Diseases Research Centre, The William Harvey Research Institute, Barts and the London, Queen Mary's School of Medicine and Dentistry, London, EC1M 6BQ, UK.
Ballinger
Anne B
AB
Vojnovic
Ivana
I
Farthing
Michael J G
MJ
Warner
Timothy D
TD
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D015232:Dinoprostone / Q000096:biosynthesis; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D019333:Endothelin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019332:Endothelin-1; D019333:Endothelin-2; D016232:Endothelins; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D015232:Dinoprostone