Deutscher, Nicole and Bataille, Frauke and Hausmann, Martin and Kiessling, Stephan and Muller-Newen, Gerhard and Leeb, Sandra N. and Herfarth, Hans and Heinrich, Peter C. and Scholmerich, Juergen and Rogler, Gerhard (2006) Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer. INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 21 (6). pp. 573-581. ISSN 0179-1958,
Full text not available from this repository. (Request a copy)Abstract
Background: Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs). Activity of IL-11 requires binding to the alpha receptor subunit (IL-11R alpha) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11R alpha is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11R alpha and its downstream signaling cascade in colonic adenoma and carcinoma. Materials and methods: The expression of IL-11R alpha in normal colonic mucosa, 11 colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In addition, IL-11R alpha-expression and IL-11R alpha-induced phosphorylation of signal transducer and activator of transcription (STAT)3 were investigated by Western blot analysis. Results: Immunohistochemistry revealed significant IL-11-R alpha expression in epithelial cells of normal colonic mucosa. In contrast, the expression of IL-11-R alpha in colon adenomas and carcinomas was either absent or only detectable in very few scattered epithelial cells. Densitometric analysis of Western blots confirmed these results, showing a decrease of IL-11R alpha-protein in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in carcinoma cells indicated functional consequences of decreased IL-11R alpha-protein expression on signal transduction. Conclusion: This study demonstrates a decrease of IL-11-R alpha-protein expression in epithelial cells isolated from colon carcinomas and adenomas compared to normal colonic mucosa and a reduced STAT3 signaling. Because of reduced binding and signal transduction, it is unlikely that therapeutically administered IL-11 would contribute to colorectal carcinoma induction and growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECOMBINANT HUMAN INTERLEUKIN-11; EPIDERMAL-GROWTH-FACTOR; ACTIVE CROHNS-DISEASE; ISCHEMIA-REPERFUSION; MOLECULAR-CLONING; SMALL-INTESTINE; CYTOKINE; RATS; CHEMOTHERAPY; CELLS; IL-11R alpha; colonic epithelial cells; colon cancer; adenoma; apoptosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Feb 2021 06:03 |
| Last Modified: | 03 Feb 2021 06:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34093 |
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