RT Journal Article
SR Electronic
T1 Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 387
OP 396
DO 10.1136/gut.47.3.387
VO 47
IS 3
A1 T Goode
A1 J O'Connell
A1 P Anton
A1 H Wong
A1 J Reeve
A1 G C O'Sullivan
A1 J K Collins
A1 F Shanahan
YR 2000
UL http://gut.bmj.com/content/47/3/387.abstract
AB BACKGROUND Substantial evidence implicates the neuropeptide substance P (SP) in mucosal immunoinflammatory responses. Autoradiographic studies have suggested a disturbance in SP receptor expression in inflammatory bowel disease (IBD).AIMS Because of technical limitations such as poor cellular resolution with autoradiography, we used molecular methods to specifically localise the cellular expression of the neurokinin-1 receptor (NK-1R) in IBD colon, and to quantitate NK-1R mRNA expression levels therein.METHODS In situ hybridisation and immunohistochemistry were used to localise NK-1R mRNA and protein, respectively, in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections. NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were quantitated by competitive reverse transcription-polymerase chain reaction.RESULTS NK-1R expression was localised to lamina propria mononuclear cells, epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal and IBD colon. No ectopic NK-1R expression was observed in IBD. However, we found increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant negative epithelial expression of NK-1R in UC, and increased expression of NK-1R in CD myenteric plexus. Quantitation of NK-1R mRNA expression in IBD colonic mucosal biopsies revealed marked upregulation of NK-1R mRNA levels compared with non-inflamed mucosal expression levels (p<0.01).CONCLUSIONS This report demonstrates the strategic localisation and upregulation of NK-1R expression in IBD colon, and thereby suggests the involvement of substance P in the pathophysiological symptoms of IBD.CDCrohn's diseaseIBDinflammatory bowel diseaseLPMClamina propria mononuclear cellsNK-1Rneurokinin 1 receptorRT-PCRreverse transcription-polymerase chain reactionqcRT-PCRquantitative competitive RT-PCRSPsubstance PUCulcerative colitisILinterleukinTNF-αtumour necrosis factor αPBSphosphate buffered saline