Increased Expression and Secretion of Interleukin-6 in Patients with Barrett’s Esophagus

Autor: Hana Holubec, Anil Prasad, Harris Bernstein, Richard E. Sampliner, Katerina Dvorakova, Bohuslav Dvorak, Harinder S. Garewal, Ronnie Fass, Jessica A. Dominguez, Claire M. Payne, Haiyan Cui, Lois Ramsey, Carol Bernstein
Rok vydání: 2004
Předmět:
Zdroj: Clinical Cancer Research. 10:2020-2028
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-0437-03
Popis: Purpose: 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-xL and Mcl-1, are also expressed in the same tissues.Experimental Design: 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-xL are present at higher levels in BE glands, with lower levels being found in duodenum or squamous epitheliumConclusions: 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.
Databáze: OpenAIRE