Proinflammatory Cytokine and Nuclear Factor Kappa-B Expression along the Inflammation-Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus

Abstract

The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Expression of Reactive Oxygen Species in Reflux Disease

“…The present study is also made on patients with mild esophagitis, classified to LA-A by the endoscopist (1). Several studies have looked at pro-inflammatory cytokines expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus and have also found a stepwise-elevated expression correlate to grade of severity of the disease (20)(21). Such association was not made in the present study for IL-1β and IL-6 at protein level, whereas gene transcript for IL-6 was increased in ERD-patients indicating somewhat small alteration may exist beyond the detections level for protein.…”

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

“…Increased NF‐κB activation is associated with elevated levels of inflammatory cytokines 47. Activation of the NF‐κB pathway increases stepwise along the spectrum of reflux esophagitis, Barrett epithelium, and adenocarcinoma, paralleling the increases in interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α 48, 49, 50. Taken together, in reflux esophagitis and Barrett's esophagus, the change of microbiomes (ie increased Gram‐negative organisms) may contribute to esophageal adenocarcinoma by inducing chronic inflammation, triggering a cascade that leads to adenocarcinoma 46…”

Glycine-extended gastrin stimulates proliferation via JAK2- and Akt-dependent NF-κB activation in Barrett’s oesophageal adenocarcinoma cells

“…We have examined the sequence of intracellular events involved in these effects of G-Gly. Previous studies have separately suggested that the activation of both the protein kinase Akt and nuclear factor-κB (NF-κB) are central to the progression of OAC (O'Riordan et al 2005;Sagatys et al 2007; and several studies have shown that Akt may be an upstream activator NF-κB signalling (Gustin et al 2004). We, and others, have previously shown that G-Gly can activate Akt signalling and in this study we have specifically examined the upstream and downstream mediators of Akt/NF-κB signalling.…”