title: Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer.
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-11Ralpha) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Ralpha is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Ralpha and its downstream signaling cascade in colonic adenoma and carcinoma.
  
  
  METHODS
  The expression of IL-11Ralpha in normal colonic mucosa, 11 colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In addition, IL-11Ralpha-expression and IL-11Ralpha-induced phosphorylation of signal transducer and activator of transcription (STAT)3 were investigated by Western blot analysis.
  
  
  RESULTS
  Immunohistochemistry revealed significant IL-11-Ralpha expression in epithelial cells of normal colonic mucosa. In contrast, the expression of IL-11-Ralpha 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-11Ralpha-protein in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in carcinoma cells indicated functional consequences of decreased IL-11Ralpha-protein expression on signal transduction.
  
  
  CONCLUSIONS
  This study demonstrates a decrease of IL-11-Ralpha-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.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Deutscher
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Martin
authors.initials: M
authors.lastname: Hausmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Kiessling
authors.forename: Gerhard
authors.initials: G
authors.lastname: Muller-Newen
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Leeb
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Peter C
authors.initials: PC
authors.lastname: Heinrich
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053703:Interleukin-11 Receptor alpha Subunit / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D053703:Interleukin-11 Receptor alpha Subunit