Increased expression of cytokines and adhesion molecules in rat chronic esophagitis.
OBJECTIVE
Cytokines and adhesion molecules regulate many inflammatory processes in several gastrointestinal diseases. The dynamics of cytokines and adhesion molecules in reflux esophagitis are unknown in detail. We examined the expression and dynamics of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, GRO/cytokine-induced neutrophil chemoattractant-2alpha (CINC-2alpha), intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18), and Mac-1 (CD11b/CD18) in rat chronic reflux esophagitis.


METHODS
Chronic acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus with a small piece of an 18-Fr Nélaton catheter. Rats were killed 3 or 21 days after operation. The levels of mRNA expression of cytokines and ICAM-1 were determined by real-time quantitative RT-PCR. Localization of adhesion molecules and cytokines was investigated by immunohistochemical staining, and numbers of LFA-1- or Mac-1-positive cells were quantified.


RESULTS
IL-1beta, TNF-alpha, MCP-1, MIP-1alpha, MIP-2, CINC-2alpha, and ICAM-1 mRNA expression was significantly increased in esophageal lesions compared with normal esophagus. There were few these cytokines- or adhesion molecule-positive cells in normal esophagus. In regions of esophagitis, numerous inflammatory leukocytes in lamina propria and the submucosal layer exhibited positive reactions for these cytokines and endothelial cells were intensely stained for ICAM-1. Numbers of LFA-1- and Mac-1-positive cells were significantly increased in rat chronic esophagitis. Treatment with rabeprazole almost completely inhibited development of chronic acid reflux esophagitis and significantly decreased expression of cytokines and ICAM-1 mRNA in esophageal tissue compared with control.


CONCLUSIONS
Cytokines and adhesion molecules play important roles in the pathogenesis of chronic reflux esophagitis in this rat model.
Hamaguchi
Masaki
M
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Fujiwara
Yasuhiro
Y
Takashima
Takashi
T
Hayakawa
Tsuyoshi
T
Sasaki
Eiji
E
Shiba
Masatsugu
M
Watanabe
Toshio
T
Tominaga
Kazunari
K
Oshitani
Nobuhide
N
Matsumoto
Takayuki
T
Higuchi
Kazuhide
K
Arakawa
Tetsuo
T
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004941:Esophagitis / Q000235:genetics* / Q000503:physiopathology* / Q000662:veterinary; D005764:Gastroesophageal Reflux / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D015815:Cell Adhesion Molecules; D016207:Cytokines