TY - JOUR
T1 - The inhibitory effects of rebamipide on cigarette smoke-induced airway mucin production
AU - Lee, Sung Yong
AU - Kang, Eun Joo
AU - Hur, Gyu Young
AU - Jung, Ki Hwan
AU - Jung, Hye Cheol
AU - Lee, Sang Yeub
AU - Kim, Je Hyeong
AU - Shin, Chol
AU - In, Kwang Ho
AU - Kang, Kyung Ho
AU - Yoo, Se Hwa
AU - Shim, Jae Jeong
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/3
Y1 - 2006/3
N2 - Cigarette smoke may be the main cause of chronic bronchitis. Exposure of cigarette smoke induces the recruitment of inflammatory cells in the airway epithelium, and release of the tumor necrosis factor α (TNFα) from airways. Previous reports have shown that cigarette smoke induces goblet cell metaplasia by activating an epidermal growth factor receptor (EGFR) cascade, and that this results in mucin production. Rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, OPC-12759) directly inhibits the production of superoxide (O2-) and inhibits proinflammatory cytokines (such as TNFα and IL-8). In the present study, we aimed to analyze the inhibitory effects of rebamipide on TNFα and EGFR activation after cigarette smoke treatment in vitro and in vivo. NCl-H292 cells and Sprague-Dawley rats were used for in vitro and in vivo studies. In vitro studies, cigarette smoke solution was found to increase TNFα secretion, and EGFR-specific tyrosine phosphorylation, and to elevate MUC5AC production. These effects were inhibited dose-dependently by pretreatment with rebamipide (MUC5AC protein levels were inhibited from 44% to 17%, P < 0.05). In vivo studies, cigarette smoke was found to cause inflammatory cell recruitment and to increase the secretion of TNFα in bronchoalveolar lavage (BAL) fluids (from 198±78 to 2270±158 pg/ml, P < 0.01). Moreover, the pretreatment of rats with rebamipide inhibited goblet cell metaplasia and TNFα secretion, dose-dependently (from 2270±158 to 1377±112 pg/ml, P < 0.05). In conclusion, the exposure of airway epithelium to cigarette smoke-induced TNFα production, neutrophil recruitment, activated EGFR, and caused MUC5AC mucin synthesis. Moreover, rebamipide was found to prevent this cigarette smoke-induced TNFα release, and mucin production.
AB - Cigarette smoke may be the main cause of chronic bronchitis. Exposure of cigarette smoke induces the recruitment of inflammatory cells in the airway epithelium, and release of the tumor necrosis factor α (TNFα) from airways. Previous reports have shown that cigarette smoke induces goblet cell metaplasia by activating an epidermal growth factor receptor (EGFR) cascade, and that this results in mucin production. Rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, OPC-12759) directly inhibits the production of superoxide (O2-) and inhibits proinflammatory cytokines (such as TNFα and IL-8). In the present study, we aimed to analyze the inhibitory effects of rebamipide on TNFα and EGFR activation after cigarette smoke treatment in vitro and in vivo. NCl-H292 cells and Sprague-Dawley rats were used for in vitro and in vivo studies. In vitro studies, cigarette smoke solution was found to increase TNFα secretion, and EGFR-specific tyrosine phosphorylation, and to elevate MUC5AC production. These effects were inhibited dose-dependently by pretreatment with rebamipide (MUC5AC protein levels were inhibited from 44% to 17%, P < 0.05). In vivo studies, cigarette smoke was found to cause inflammatory cell recruitment and to increase the secretion of TNFα in bronchoalveolar lavage (BAL) fluids (from 198±78 to 2270±158 pg/ml, P < 0.01). Moreover, the pretreatment of rats with rebamipide inhibited goblet cell metaplasia and TNFα secretion, dose-dependently (from 2270±158 to 1377±112 pg/ml, P < 0.05). In conclusion, the exposure of airway epithelium to cigarette smoke-induced TNFα production, neutrophil recruitment, activated EGFR, and caused MUC5AC mucin synthesis. Moreover, rebamipide was found to prevent this cigarette smoke-induced TNFα release, and mucin production.
KW - Epidermal growth factor receptor
KW - Mucin
KW - Rebamipide
KW - Smoking
KW - TNFα
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U2 - 10.1016/j.rmed.2005.06.006
DO - 10.1016/j.rmed.2005.06.006
M3 - Article
C2 - 16039106
AN - SCOPUS:32644434585
VL - 100
SP - 503
EP - 511
JO - Respiratory Medicine
JF - Respiratory Medicine
SN - 0954-6111
IS - 3
ER -