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New aspects concerning ulcerative colitis and colonic carcinoma: analysis of levels of neuropeptides, neurotrophins, and TNFalpha/TNF receptor in plasma and mucosa in parallel with histological evaluation of the intestine
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2008 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 10, 1331-1340 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The levels of neuropeptides, neurotrophins, and TNFalpha (TNFalpha)/TNF receptor in plasma and mucosa for patients with ulcerative colitis (UC) and colonic carcinoma, and concerning plasma also for healthy controls, were examined. Moreover, the relationships between the different substances and the influence of mucosal derangement on the levels were analyzed.

METHODS: The levels of VIP, SP, CGRP, BDNF, NGF, and TNFalpha/TNF receptor 1 were measured using ELISA/EIA.

RESULTS: Patients with UC demonstrated the highest levels of all analyzed substances in plasma, with the exception of BDNF. However, there were differences within the UC group, patients treated with corticosteroids, and/or nonsteroid antiinflammatory/immunosuppressive treatment having higher plasma levels than those not given these treatments. Patients with colonic carcinoma showed higher SP and TNF receptor 1 levels in plasma compared to healthy controls. Concerning mucosa, the levels of almost all analyzed substances were elevated for patients with UC compared to noncancerous mucosa of colonic carcinoma patients. There were correlations between many of the substances in both plasma and mucosa, especially concerning the 3 neuropeptides examined. There were also marked associations with mucosa derangement.

CONCLUSIONS: Via analysis of correlations for the respective patients and via comparisons between the different patient groups, new and original information was obtained. Interestingly, the degree of mucosal affection was markedly correlated with tissue levels of the substances and the treatments were found to be of importance concerning plasma but not tissue levels of these. Combined plasma analysis of neuropeptides, neurotrophins, and TNF receptor 1 may help to distinguish UC and colonic carcinoma patients.

Place, publisher, year, edition, pages
2008. Vol. 14, no 10, 1331-1340 p.
URN: urn:nbn:se:umu:diva-19265DOI: 10.1002/ibd.20487PubMedID: 18452198OAI: diva2:201652
Available from: 2009-03-05 Created: 2009-03-05 Last updated: 2010-06-24Bibliographically approved
In thesis
1. The neuronal and non-neuronal substance P, VIP and cholinergic systems in the colon in ulcerative colitis
Open this publication in new window or tab >>The neuronal and non-neuronal substance P, VIP and cholinergic systems in the colon in ulcerative colitis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Neuropeptides, especially vasoactive intestinal peptide (VIP) and substance P (SP), have long been considered to play key roles in UC. Among other effects, these neuropeptides have trophic and growth-modulating as well as wound-healing effects. Furthermore, whilst VIP has anti-inflammatory properties, SP has pro-inflammatory effects. It is generally assumed that the main source of SP and VIP in the intestine is the tissue innervation. It is not known whether or not they are produced in the epithelial layer. The details concerning the expressions of their receptors in UC are also, to a great extent, unclear. Apart from the occurrence of peptidergic systems in the intestine, there are also neuronal as well as non-neuronal cholinergic systems. The pattern concerning the latter is unknown with respect to UC.

The studies in this thesis aimed to investigate the expression of SP and VIP and their major receptors (NK-1R and VPAC1) in UC colon, compared to non-UC colon. The main emphasis was devoted to the epithelium. A second aim was to examine for levels of these neuropeptides in blood plasma in UC. Another aim was to examine for the non-neuronal cholinergic system in UC, thus, to investigate whether there is acetylcholine production outside nerves in the UC colon. Methods used in the thesis were immunohistochemistry, in situ hybridization, enzyme immunosorbent assay, and in vitro receptor autoradiography.

For the first time, mRNA for VIP and SP has here been found in the colonic epithelium. That was especially noted in UC mucosa showing a rather normal morphology, and in non-UC mucosa. Marked derangement of the mucosa was found to lead to a distinct decrease in VIP binding, and also a decrease in the expression level of VIP receptor VPAC1 in the epithelium. In general, there was an upregulation of the SP receptor NK-1R in the epithelium when the mucosa was deranged. The plasma levels of SP and VIP were higher for UC patients compared to healthy controls. There were marked correlations between the levels of the peptides in plasma, their levels in the mucosa and the degree of mucosal derangement/inflammation. A pronounced nonneuronal cholinergic system was found in both UC and non-UC colon. Certain changes occurred in this system in response to inflammation/derangement in UC. The present study shows unexpectedly that expressions for VIP and SP are not only related to the nerve structures and the inflammatory cells. The downregulation of VPAC1 expression, and the tendencies of upregulation of NK-1R expression levels when there is marked tissue derangement, may be a drawback for the intestinal function. The study also shows that there is a marked release of neuropeptides to the bloodstream in parallel with a marked derangement of the mucosa in UC. The cholinergic effects in the UC colon appear not only to be associated with nerverelated effects, but also effects of acetylcholine produced in local non-neuronal cells. The thesis shows that local productions for not only acetylcholine, but also SP and VIP, occur to a larger extent than previously considered.

Place, publisher, year, edition, pages
Umeå: Institutionen för integrativ medicinsk biologi, 2009. 62 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1248
ulcerative colitis, neuropeptides, substance P, VIP, non-neuronal cholinergic system
National Category
Cell and Molecular Biology Surgery
Research subject
Human Anatomy
urn:nbn:se:umu:diva-19946 (URN)978-91-7264-731-2 (ISBN)
Public defence
2009-04-03, BiA 201, Biologihuset, Umeå, 09:00 (Swedish)
Available from: 2009-03-13 Created: 2009-03-12 Last updated: 2010-04-15Bibliographically approved

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