Zusammenfassung
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 ...
Zusammenfassung
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.
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