Loading in 2 Seconds...
Loading in 2 Seconds...
Regulation of epithelial syndecan-1 expression by inflammatory cytokines. Richard M. Day, Tracey J. Mitchell, Stella C. Knight, Alastair Forbes Cytokine 21 (2003) 224–233. Introduction. Inflammatory bowel disease (IBD).
Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.
Richard M. Day, Tracey J. Mitchell, Stella C. Knight, Alastair Forbes
Cytokine 21 (2003) 224–233
Inflammatory bowel disease (IBD) refers to the condition that results when cells involved in inflammation and immune response are called into the lining of the GI tract.
IBD is characterized by chronic intestinal inflammation that results in clinical symptoms such as diarrhea, bleeding, abdominal pain, fever, joint pain, and weight loss.
Dysregulation of epithelial glycosaminoglycans (GAGs) occurs in IBD
Syndecans are a class of heparan sulphate proteoglycans that mediate both cell adhesion and growth factor binding via GAG side chains.
The best characterized of the four syndeacan core proteins binding to variety of components of extracellular matrix, including collagen type1 ,3,5 and fibronectin.
Syndecan-1 may regulate ligand-dependent activation of cell surface growth factor at two dimernsional surface of plasma membrane
Fibroblast growth factor(bFGF), hepatocyte growth factor,platelet-derived growth factor,vascular endothelial growth factor,and etc.
Reduced expression of syndecan-1 observed in IBD results from the increased presence of inflammatory cytokines.
RNA extraction and amplification by reverse transcription-polymerase chain reaction
5 ng/ml TNF-a
75 ng/ml TNF-a
IgG1 isotype control
B,C,D HT29 cell
E T84 cell
Above 86% for all concentrations of cytokine studied.
HT29 cell treated with 5 ng/ml TNF-a for the various time
HT29 cell treated with TNF-a, IL-1b and IL-6 for 24h
Syndecan-1 expression reduced to 49.7%
Syndecan-1 expression reduced to 64.3%
Cytokine stimulation induced syndecan-1 shedding from the cell surface
Co-culture HT29 cell and PBMC
PBMC endogenous inflammatory cytokine
PMA increase syndecan-1 suppression
Epithelial expression of syndecan-1 is down-regulated in the mucosa of the patients with IBD
other model without inflammation
The expression of
Increased syndecan-1 expression during wound repair is thought to facilitate growth factor binding and wound healing.
The reduced expression in IBD maybe related to the presence of inflammatory cytokines in mucosa.
Stable expression of syndecan-1
TNF-a, IL-1b and IL6 stimulate
Reduced Syndecan-1 expression
IL-6 to cause a reduction of syndecan-1 expression in murine B-lymphoid cells cell-type specific
Inflammatory cytokine ex. TNF-a IL-1
Expression of E-cadherin is dependent on syndecan-1 expression and vice versa.
Cytokine induce loss of cell-adhesion through reduced syndecan-1 and/or E-caderine destablizes the epithelial barrier.
Increase intestinal permeability in IBD
Shedding of syndeacan-1 ectodomain into the culture medium of HT29 cell monolayers was significantly increase following the addition of TNF-a .
The increase syndecan-1, shedding following stimulation correlated with the loss of membrane syndecan-1 expression
Some syndecan-1 detected may also have been released as the intact proteoglycan from dead cell
Reduced syndecan-1 expression
Increased ICAM-1 expression
+ TNF-a and IL-1b
The loss of GAG expression in p’t with IBD is associated with increased density of TNF-a
This study demonstrates dysregulation of epithelial syndecan-1 expression by inflammatory cytokines and may have implications for mucosal ulcer healing.
Inflammatory bowel disease refers to the condition that results when cells involved in inflammation and immune response are called into the lining of the GI tract. This infiltration thickens the bowel lining and interferes with absorption and motility (the ability of the bowel to contract and move food). With abnormal ability to contract and abnormal ability to absorb, the bowel’s function is disrupted. Chronic vomiting results if the infiltration is in the stomach or higher areas of the small intestine. A watery diarrhea with weight loss results if the infiltration is in the lower small intestine. A mucous diarrhea with fresh blood (colitis) results if the infiltration occurs in the large intestine. Of course, the entire tract from top to bottom may be involved. Many people confuse Inflammatory Bowel Disease with “Irritable Bowel Syndrome,” a stress-related diarrhea problem. Treatment for “IBS” is aimed at stress; it is a completely different condition from “IBD.”
These symptoms can range from mild to severe, and may gradually and subtly develop from an initial minor discomfort, or may present themselves suddenly with acute intensity.