Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease

Michalski, Christoph W; Autschbach, Frank; Selvaggi, Federico; Shi, Xin; Di Mola, Fabio Francesco; Roggo, Antoine; Müller, Michael W; Di Sebastiano, Pierluigi; Büchler, Markus W; Giese, Thomas; Friess, Helmut (2007). Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease. American journal of surgery, 193(4), pp. 476-81. Amsterdam: Elsevier Science 10.1016/j.amjsurg.2006.08.075

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BACKGROUND: Neuropeptides, such as substance P (SP), are mediators of neurogenic inflammation and play an important role in inflammatory disorders. To further investigate the role of the SP pathway in inflammatory bowel disease (IBD), we analyzed the following in normal intestinal tissue specimens and in tissue specimens from patients with Crohn's disease (CD) and ulcerative colitis (UC): neurokinin receptor-1 (NK-1R); its isoforms (NK-1R-L and NK-1R-S); its ligand SP, encoded by preprotachykinin-A (PPT-A); and the SP-degradation enzyme, neutral endopeptidase (NEP). METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to simultaneously determine the expression of NK-1R-L, NK-1R-S, and PPT-A. Protein levels of NK-1R and NEP were determined by immunoblot analysis. RESULTS: In noninflamed small-bowel tissue samples of CD patients, PPT-A mRNA expression was significantly increased, whereas there was no difference between inflamed or noninflamed UC and normal intestinal tissue samples. Examining subgroups of diverse intestinal segments from CD and UC samples with various levels of inflammation revealed no differences in NK-1R-L and NK-1R-S mRNA expression, whereas there was a tendency toward overall lower NK-1R-S mRNA copy numbers. Immunoblot analysis showed upregulation of NK-1R protein levels in cases of IBD, with more pronounced enhancement in cases of CD than in UC. For NEP, there were no differences in protein levels in normal, CD, and UC intestinal tissues. COMMENTS: These observations suggest a contribution of SP and its receptor, NK-1R, in the local inflammatory reaction in IBD and particularly in ileal CD. Moreover, significant upregulation of PPT-A mRNA in the noninflamed ileum of these patients suggests an influence of inflamed intestines on their healthy counterparts.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Legal Medicine > Forensic Medicine

UniBE Contributor:

Roggo, Anton

ISSN:

0002-9610

ISBN:

17368292

Publisher:

Elsevier Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:56

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.1016/j.amjsurg.2006.08.075

PubMed ID:

17368292

Web of Science ID:

000245465100012

URI:

https://boris.unibe.ch/id/eprint/23901 (FactScience: 45089)

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