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Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

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 α receptor subunit (IL-11Rα) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Rα is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Rα and its downstream signaling cascade in colonic adenoma and carcinoma.

Materials and methods

The expression of IL-11Rα in normal colonic mucosa, 11 colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In addition, IL-11Rα-expression and IL-11Rα-induced phosphorylation of signal transducer and activator of transcription (STAT)3 were investigated by Western blot analysis.

Results

Immunohistochemistry revealed significant IL-11-Rα expression in epithelial cells of normal colonic mucosa. In contrast, the expression of IL-11-Rα 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-11Rα-protein in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in carcinoma cells indicated functional consequences of decreased IL-11Rα-protein expression on signal transduction.

Conclusion

This study demonstrates a decrease of IL-11-Rα-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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Abbreviations

Ab:

antibody

CEC:

human primary colonic epithelial cells

FITC:

fluoresceine isothiocyanate

G3PDH:

glyceraldehyde-3-phosphate-dehydrogenase

IBD:

inflammatory bowel disease

IL-11:

interleukin-11

IL-11Rα:

interleukin-11 receptor alpha-chain

Jak:

Janus kinase

mAb:

monoclonal antibody

STAT:

signal transducer and activator of transcription

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (SFB585, SFB542) and the BMBF Kompetenznetzwerk: Chronisch-entzündliche Darmerkrankungen. We deeply appreciate the support by all patients agreeing to the use of surgical specimen for this study. We thank the Departments of Surgery and the Institute of Pathology, University of Regensburg, for excellent cooperation. We would also like to thank Sylvia Kellermeier for expert technical assistance. The manuscript contains original unpublished work and is not being submitted for publication elsewhere at the same time. There are no financial or other relationships that might lead to a conflict of interest. The manuscript has been read and approved by all authors, the requirements for authorship have been met and each author believes that the manuscript represents honest work.

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Authors and Affiliations

  1. Department of Internal Medicine I, University of Regensburg, 93042, Regensburg, Germany

    Nicole Deutscher, Martin Hausmann, Stephan Kiessling, Sandra N. Leeb, Hans Herfarth, Jürgen Schölmerich & Gerhard Rogler

  2. Institute of Pathology, University of Regensburg, Regensburg, Germany

    Frauke Bataille

  3. Institute of Biochemistry, RWTH, Aachen, Germany

    Gerhard Muller-Newen & Peter C. Heinrich

Authors
  1. Nicole Deutscher
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  2. Frauke Bataille
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  3. Martin Hausmann
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  8. Peter C. Heinrich
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  9. Jürgen Schölmerich
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  10. Gerhard Rogler
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Corresponding author

Correspondence to Gerhard Rogler.

Additional information

N. Deutscher and F. Bataille contributed equally

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Deutscher, N., Bataille, F., Hausmann, M. et al. Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer. Int J Colorectal Dis 21, 573–581 (2006). https://doi.org/10.1007/s00384-005-0055-8

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