title: 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.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Shunkaikai Inoue Hospital, Nagasaki, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Isomoto
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Yusei
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nishi
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akazawa
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Omagari
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mizuta
authors.forename: Ikuo
authors.initials: I
authors.lastname: Murata
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004945:Esophagoscopy; D004947:Esophagus / Q000378:metabolism; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger