Role of interleukin-6 in Barrett's esophagus pathogenesis

Abstract

Barrett's esophagus (BE) is a metaplastic lesion of the distal esophagus arising as a consequence of chronic gastroesophageal reflux disease. Multiple studies show that BE is associated with increased risk of esophageal adenocarcinoma (EAC). Epidemiological studies and animal models demonstrate that chronic inflammation triggered by repeated exposure to refluxate predisposes to the development of BE and EAC. The chronic inflammation is associated with cytokine alterations. Interleukin 6 (IL-6) is a cytokine that stimulates cell proliferation and apoptosis resistance is frequently increased in different cancers. Importantly, IL-6 and transcriptional factor signal transducer and activator of transcription 3 (STAT3) that is activated by IL-6 are also increased in BE and EAC. This review critically appraises the role of IL-6/STAT3 pathway in progression of BE to EAC from the published evidence currently available.

Keywords: Apoptosis; Barrett’s esophagus; Bile acids; Inflammation; Interleukin 6.

Figure 1

Interleukin 6 signaling scheme of the interleukin 6/signal transducer and activator of transcription 3 signaling pathway. IL-6: Interleukin 6; STAT3: Signal transducer and activator of transcription 3; sIL-6R: Soluble IL-6 receptor; IL-6R: IL-6 receptor; JAK: Janus kinase; MAPK: Mitogen-activated protein kinase; VEGF: Vascular endothelial growth factor; ANG: Angiopoietin.

Figure 2

Apoptosis and the signaling pathways activated by bile acids. EGFR: Epidermal growth factor receptor; MAPK: Mitogen-activated protein kinase; IL-6: Interleukin 6; STAT3: Signal transducer and activator of transcription 3; COX: Cyclooxygenase; LOX: Lipooxygenase; IKK: IκB kinase; ROS: Reactive oxygen species; NF-κB: Nuclear factor kappa B; PLA2: Phospholipase A2; NAPDH: Nicotinamide adenine dinucleotide phosphate; ERK: Extracellular-signal-regulated kinase; FASR: FAS receptor; TRAILR: TRAIL receptor.