Impact of endoscopically minimal involvement on IL-8 mRNA expression in esophageal mucosa of patients with non-erosive reflux disease.
OBJECTIVE
Little has been known about the pathogenesis of non-erosive reflux disease (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development and progression of gastroesophogeal reflux disease (GERD). The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes.


METHODS
We studied 26 patients with NERD and 13 asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction (PCR). We also examined mRNA expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The patients were endoscopically classified into grade M (mucosal color changes without visible mucosal break) and N (neither minimal involvement nor mucosal break) of the modified Los Angeles classification.


RESULTS
The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls. There was a significant difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa.


CONCLUSIONS
Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.
Kanazawa
Yusei
Y
Second Department of Internal Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan.
Isomoto
Hajime
H
Wen
Chun-Yang
CY
Wang
Ai-Ping
AP
Saenko
Vladimir A
VA
Ohtsuru
Akira
A
Takeshima
Fuminao
F
Omagari
Katsuhisa
K
Mizuta
Yohei
Y
Murata
Ikuo
I
Yamashita
Shunichi
S
Kohno
Shigeru
S
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D001483:Base Sequence; D017931:DNA Primers; D016145:Endoscopy, Digestive System; D005260:Female; D005764:Gastroesophageal Reflux / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D016481:Helicobacter Infections / Q000453:epidemiology; D016480:Helicobacter pylori; D006551:Hernia, Hiatal / Q000453:epidemiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking
D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger