This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dvorakova, K. Articles by Garewal, H. Search for Related Content PubMed PubMed Citation Articles by Dvorakova, K. Articles by Garewal, H.

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

¹ Department of Microbiology and Immunology, ² Arizona Cancer Center, ³ Department of Internal Medicine, ⁴ Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, Arizona, and ⁵ Section of Hematology/Oncology, ⁶ Department of Pathology, Southern Arizona VA Health Care System, Tucson, Arizona

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-x_L 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-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.

This article has been cited by other articles:

				L.M.G. Moons, J.G. Kusters, J.H.M. van Delft, E.J. Kuipers, R. Gottschalk, H. Geldof, W.A. Bode, J. Stoof, A.H.M. van Vliet, H.B. Ketelslegers, et al. A pro-inflammatory genotype predisposes to Barrett's esophagus Carcinogenesis, May 1, 2008; 29(5): 926 - 931. [Abstract] [Full Text] [PDF]

				K. Dvorak, M. Chavarria, C. M. Payne, L. Ramsey, C. Crowley-Weber, B. Dvorakova, B. Dvorak, H. Bernstein, H. Holubec, R. E. Sampliner, et al. Activation of the Interleukin-6/STAT3 Antiapoptotic Pathway in Esophageal Cells by Bile Acids and Low pH: Relevance to Barrett's Esophagus Clin. Cancer Res., September 15, 2007; 13(18): 5305 - 5313. [Abstract] [Full Text] [PDF]

				K. Dvorak, C. M Payne, M. Chavarria, L. Ramsey, B. Dvorakova, H. Bernstein, H. Holubec, R. E Sampliner, N. Guy, A. Condon, et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus Gut, June 1, 2007; 56(6): 763 - 771. [Abstract] [Full Text] [PDF]