title: Increased expression and secretion of interleukin-6 in patients with Barrett's esophagus.
abstract: OBJECTIVE
  Barrett's esophagus (BE) is a common premalignant lesion of the distal part of the esophagus that arises as a consequence of chronic duodenogastroesophageal reflux. Interleukin (IL)-6 is a pleiotropic cytokine that regulates immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. IL-6 has been shown to inhibit apoptosis. The major aim of this study was to evaluate expression of IL-6 in BE at the protein and mRNA levels. In addition, we tested whether proteins that are associated with IL-6 signaling, phosphorylated signal transducer and activator of transcription 3 and two antiapoptotic proteins, Bcl-x(L) and Mcl-1, are also expressed in the same tissues.
  
  
  METHODS
  Biopsies of duodenum, BE, and squamous epithelium were evaluated by using a human cytokine protein array, ELISA, real-time PCR, and immunohistochemistry.
  
  
  RESULTS
  Increased IL-6 levels were found to be secreted from BE tissue compared with duodenum or squamous epithelium from sites adjacent or 5 cm away from the BE lesion. IL-6 mRNA was also elevated in BE compared with duodenum or squamous epithelium in five of seven patients. Immunohistochemical studies confirmed IL-6 expression in intestinal glandular epithelium in BE tissue. Activated signal transducer and activator of transcription 3, Mcl-1, and Bcl-x(L) are present at higher levels in BE glands, with lower levels being found in duodenum or squamous epithelium
  
  
  CONCLUSIONS
  These data, taken together, suggest that elevated IL-6 levels in BE may contribute to the development of apoptosis resistance, thereby placing this epithelium at higher risk of developing malignancy.
authors.affiliation: Department of Microbiology and Immunology, Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85723, USA.
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorakova
authors.forename: Claire M
authors.initials: CM
authors.lastname: Payne
authors.forename: Lois
authors.initials: L
authors.lastname: Ramsey
authors.forename: Hana
authors.initials: H
authors.lastname: Holubec
authors.forename: Richard
authors.initials: R
authors.lastname: Sampliner
authors.forename: Jessica
authors.initials: J
authors.lastname: Dominguez
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
authors.forename: Harris
authors.initials: H
authors.lastname: Bernstein
authors.forename: Carol
authors.initials: C
authors.lastname: Bernstein
authors.forename: Anil
authors.initials: A
authors.lastname: Prasad
authors.forename: Ronnie
authors.initials: R
authors.lastname: Fass
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.forename: Harinder
authors.initials: H
authors.lastname: Garewal
mesh_terms: D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000276:immunology; D002471:Cell Transformation, Neoplastic; D004386:Duodenum / Q000276:immunology; D004938:Esophageal Neoplasms / Q000453:epidemiology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015850:Interleukin-6