Increased expression and secretion of interleukin-6 in patients with Barrett's esophagus.
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.
Dvorakova
Katerina
K
Department of Microbiology and Immunology, Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85723, USA.
Payne
Claire M
CM
Ramsey
Lois
L
Holubec
Hana
H
Sampliner
Richard
R
Dominguez
Jessica
J
Dvorak
Bohuslav
B
Bernstein
Harris
H
Bernstein
Carol
C
Prasad
Anil
A
Fass
Ronnie
R
Cui
Haiyan
H
Garewal
Harinder
H
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
D015850:Interleukin-6