Response to TNF-α Is Increasing Along with the Progression in Barrett's Esophagus

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2017 Nov 1

PMID 29086334

Citations 5

Authors

Olga Chemnitzer

Katharina Gotzel

Luisa Maurer

Arne Dietrich

Uwe Eichfeld

Orestis Lyros

Boris Jansen-Winkeln

Albrecht Hoffmeister

Ines Gockel

Rene Thieme

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Barrett's esophagus, a metaplasia resulting from a long-standing reflux disease, and its progression to esophageal adenocarcinoma (EAC) are characterized by activation of pro-inflammatory pathways, induced by cytokines.

Methods: An in vitro cell culture system representing the sequence of squamous epithelium (EPC1 and EPC2), Barrett's metaplasia (CP-A), dysplasia (CP-B) to EAC (OE33 and OE19) was used to investigate TNF-α-mediated induction of interleukin-8 (IL-8).

Results: IL-6 and IL-8 expressions are increasing with the progression of Barrett's esophagus, with the highest expression of both cytokines in the dysplastic cell line CP-B. IL-8 expression in EAC cells was approx. 4.4-fold (OE33) and eightfold (OE19) higher in EAC cells than in squamous epithelium cells (EPC1 and EPC2). The pro-inflammatory cytokine TNF-α increased IL-8 expression in a time-, concentration-, and stage-specific manner. Furthermore, TNF-α changed the EMT marker profile in OE33 cells by decreasing the epithelial marker E-cadherin and increasing the mesenchymal marker vimentin. The anti-inflammatory compound curcumin was able to repress proliferation and to activate apoptosis in both EAC cell lines.

Conclusion: The increased basal expression levels of IL-8 with the progression of Barrett's esophagus constrain NFκB activation and its contribution in the manifestation of Barrett's esophagus. An anti-inflammatory compound, such as curcumin, could create an anti-inflammatory microenvironment and thus potentially support an increase chemosensitivity in EAC cells.

Citing Articles

Cytokine Interaction With Cancer-Associated Fibroblasts in Esophageal Cancer.

Hassan M, Cwidak N, Awasthi N, von Holzen U Cancer Control. 2022; 29:10732748221078470.

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Role of Obesity, Physical Exercise, Adipose Tissue-Skeletal Muscle Crosstalk and Molecular Advances in Barrett's Esophagus and Esophageal Adenocarcinoma.

Bilski J, Pinkas M, Wojcik-Grzybek D, Magierowski M, Korbut E, Mazur-Bialy A Int J Mol Sci. 2022; 23(7).

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Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells.

Storz L, Walther P, Chemnitzer O, Lyros O, Niebisch S, Mehdorn M Cancers (Basel). 2021; 13(11).

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Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche.

Han P, Cao P, Hu S, Kong K, Deng Y, Zhao B Cancer Manag Res. 2020; 12:5857-5879.

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In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett's sequence.

Gotzel K, Chemnitzer O, Maurer L, Dietrich A, Eichfeld U, Lyros O BMC Gastroenterol. 2019; 19(1):38.

PMID: 30841855 PMC: 6404335. DOI: 10.1186/s12876-019-0957-5.

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