Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease.

Abstract

OBJECTIVE:

Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression.

METHODS:

We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1.

RESULTS:

The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells.

CONCLUSIONS:

Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

• Authors: Hajime Isomoto, Vladimir A Saenko, Yusei Kanazawa, Yoshito Nishi, Akira Ohtsuru, Kenichiro Inoue, Yuko Akazawa, Fuminao Takeshima, Katsuhisa Omagari, Masanobu Miyazaki, Yohei Mizuta, Ikuo Murata, Shunichi Yamashita, Shigeru Kohno
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 99 Issue 4 Pg. 589-97 (Apr 2004) ISSN: 0002-9270 [Print] United States
• PMID: 15089887 (Publication Type: Journal Article)

Chemical References

• Interleukin-8
• NF-kappa B
• RNA, Messenger

Topics

• Adult
• Aged
• Aged, 80 and over
• Esophagoscopy
• Esophagus (metabolism)
• Female
• Gastroesophageal Reflux (metabolism, prevention & control)
• Humans
• Immunohistochemistry
• Interleukin-8 (biosynthesis, genetics)
• Male
• Middle Aged
• Mucous Membrane (metabolism)
• NF-kappa B (physiology)
• RNA, Messenger (analysis, biosynthesis)