| Tumor necrosis factor-α and Muc2 mucin play major roles in disease onset and progression in dextran sodium sulphate-induced colitis. | |
| | |
MedLine Citation:
|
PMID: 21949848 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The sequential events and the inflammatory mediators that characterize disease onset and progression of ulcerative colitis (UC) are not well known. In this study, we evaluated the early pathologic events in the pathogenesis of colonic ulcers in rats treated with dextran sodium sulfate (DSS). Following a lag phase, day 5 of DSS treatment was found clinically most critical as disease activity index (DAI) exhibited an exponential rise with severe weight loss and rectal bleeding. Surprisingly, on days 1-2, colonic TNF-α expression (70-80-fold) and tissue protein (50-fold) were increased, whereas IL-1β only increased on days 7-9 (60-90-fold). Days 3-6 of DSS treatment were characterized by a prominent down regulation in the expression of regulatory cytokines (40-fold for IL-10 and TGFβ) and mucin genes (15-18 fold for Muc2 and Muc3) concomitant with depletion of goblet cell and adherent mucin. Remarkably, treatment with TNF-α neutralizing antibody markedly altered DSS injury with reduced DAI, restoration of the adherent and goblet cell mucin and IL-1β and mucin gene expression. We conclude that early onset colitis is dependent on TNF-α that preceded depletion of adherent and goblet cell mucin prior to epithelial cell damage and these biomarkers can be used as therapeutic targets for UC. |
| | |
Authors:
|
Poonam Dharmani; Pearl Leung; Kris Chadee |
Related Documents
:
|
20427238 - Vitamin d: modulator of the immune system. 20558288 - Immune senescence in aged nonhuman primates. 16011518 - Age, gender and litter-related variation in t-lymphocyte cytokine production in young p... 10657488 - Age-related changes in the modulatory action of gastrin-releasing peptide, neuropeptide... 12427128 - Platelet-derived growth factor-d expression in developing and mature human kidneys. 11181108 - Human alveolar macrophage responses to air pollution particulates are associated with i... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-09-19 |
Journal Detail:
|
Title: PloS one Volume: 6 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2011 |
Date Detail:
|
Created Date: 2011-09-28 Completed Date: 2012-02-03 Revised Date: 2012-05-07 |
Medline Journal Info:
|
Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
|
Languages: eng Pagination: e25058 Citation Subset: IM |
Affiliation:
|
Department of Microbiology, Immunology and Infectious Diseases, Gastrointestinal Research Group, Health Sciences Centre, University of Calgary, Calgary, Alberta, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Cells, Cultured Colitis / chemically induced, metabolism*, pathology* Dextran Sulfate / toxicity* Disease Progression Epithelial Cells / metabolism Goblet Cells / metabolism Immunoenzyme Techniques Interleukin-10 / metabolism Male Mucin-2 / genetics, metabolism* RNA, Messenger / genetics Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Tumor Necrosis Factor-alpha / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
|
0/Muc2 protein, mouse; 0/Mucin-2; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10; 9042-14-2/Dextran Sulfate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Diverse arrangement of photosynthetic gene clusters in aerobic anoxygenic phototrophic bacteria.
Next Document: Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes fr...