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Inflammatory bowel disease
Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation
  1. T Goodea,
  2. J O'Connella,
  3. P Antonc,
  4. H Wongc,
  5. J Reevec,
  6. G C O'Sullivanb,
  7. J K Collinsa,
  8. F Shanahana
  1. 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
  1. 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

    • https://doi.org/10.1136/gut.47.3.387

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    • 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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