Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation (original) (raw)

Inflammatory bowel disease

Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation

T Goodea,
J O'Connella,
P Antonc,
H Wongc,
J Reevec,
G C O'Sullivanb,
J K Collinsa,
F Shanahana
aDepartment of Medicine, National University of Ireland, Cork, Ireland, bDepartment of Surgery, National University of Ireland, Cork, Ireland, cDivision of Digestive Diseases, University of California at Los Angeles, 675 Charles E Young Drive S, Los Angeles, CA 90095, USA
F Shanahan, Department of Medicine, Clinical Sciences Building, University Hospital, Cork, Ireland. Email:fshanahan{at}bureau.ucc.ie

Abstract

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.

substance P
neurokinin-1 receptor
inflammatory bowel disease
Abbreviations used in this paper

CD
Crohn's disease
IBD
inflammatory bowel disease
LPMC
lamina propria mononuclear cells
NK-1R
neurokinin 1 receptor
RT-PCR
reverse transcription-polymerase chain reaction
qcRT-PCR
quantitative competitive RT-PCR
SP
substance P
UC
ulcerative colitis
IL
interleukin
TNF-α
tumour necrosis factor α
PBS
phosphate buffered saline

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