Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells.
BACKGROUND
Helicobacter pylori CagA dysregulates cell signaling pathways and leads to targeted transcriptional up-regulation of genes implicated in gastric cell injury. The aim of this study was to determine the effects of rebamipide on CagA-induced effects on gastric epithelial cells. We investigated the effects of rebamipide treatment (pre- or post-treatment before or after CagA transfection) on CagA-induced gastric cell injury.


METHODS
We evaluated the morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization by confocal microscopy, IL-8 production by ELISA, and NF-κB activation by luciferase assay in AGS gastric epithelial cells and MDCK cells.


RESULTS
Transfection of CagA into gastric epithelial cells induced morphologic changes (hummingbird phenotype), ZO-1 mislocalization, and IL-8 production in gastric epithelial cells. Pre-treatment with rebamipide inhibits CagA-induced effects on gastric epithelial cells, including morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization, IL-8 production, and NF-κB activity.


CONCLUSIONS
These results suggest that rebamipide might have a potential role in the protection of H. pylori CagA-induced effects on gastric epithelial cells.
Lee
Kyung Hwa
KH
Department of Pathology, Pusan National University School of Medicine and Pusan National University Hospital, Pusan National University, Seo-Gu, Busan, Republic of Korea.
Kim
Jee-Yeon
JY
Kim
Woo-Kyung
WK
Shin
Dong-Hun
DH
Choi
Kyung-Un
KU
Kim
Dae Whan
DW
Lee
Woo-Jeong
WJ
Choi
Jin-Hwa
JH
Lee
Soo Han
SH
Kim
Gwang Ha
GH
Song
Geun Am
GA
Jeon
Tae Young
TY
Kim
Chi Dae
CD
Hong
Ki Whan
KW
Park
Do Youn
DY
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000633:toxicity*; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology* / Q000187:drug effects; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
D000897:Anti-Ulcer Agents; D000942:Antigens, Bacterial; D000975:Antioxidants; D001426:Bacterial Proteins; D016209:Interleukin-8; D008565:Membrane Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; D015363:Quinolones; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C080866:cagA protein, Helicobacter pylori; C052785:rebamipide; D000409:Alanine