Interleukin-13 And Transforming Growth Factor Beta Synergise In The Pathogenesis Of Human Intestinal Fistulae
GUT(2013)
Abstract
Objective Epithelial to mesenchymal transition (EMT) seems to play an important role in the pathogenesis of fistulae, a common clinical complication of Crohn's disease (CD). TGF beta and interleukin-13 (IL-13) have been correlated with the onset of EMT-associated organ fibrosis and high levels of TGF beta have been shown in transitional cells (TCs) lining CD fistula tracts. This study investigated whether IL-13 could be involved in the pathogenesis of CD-associated fistulae.Design Protein or mRNA levels in HT29 intestinal epithelial cells (IECs) or colonic lamina propria fibroblasts (CLPFs) were studied by western blotting or real-time PCR. CLPFs were isolated from non-inflammatory disease controls or patients with CD with or without fistulae and IL-13 levels were analysed in surgically removed fistula specimens by immunohistochemistry.Results TGF beta induced IL-13 secretion in CLPFs from patients with fistulising CD. In fistula specimens high levels of IL-13 were detected in TCs covering fistula tracts. In HT29 IEC monolayers, IL-13 induced SLUG and beta 6-integrin mRNA, which are associated with cell invasion. HT29 spheroids completely disintegrated when treated with TGF beta for 7 days, whereas IL-13-treated spheroids did not show morphological changes. Here, TGF beta induced mRNA expression of SNAIL1 and IL-13, whereas IL-13 elevated SLUG and beta 6-integrin mRNA. An anti-IL-13 antibody was able to prevent IL-13-induced SLUG expression in HT29 IECs.Conclusions TGF beta induces IL-13 expression and an EMT-like phenotype of IECs, while IL-13 promotes the expression of genes associated with cell invasion. These findings suggest that TGF beta and IL-13 play a synergistic role in the pathogenesis of fistulae and inhibition of IL-13 might represent a novel therapeutic approach for fistula treatment.
MoreTranslated text
Key words
human intestinal fistulae,pathogenesis
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined