Indometacin up-regulates TFF2 expression in gastric epithelial cells.
BACKGROUND
Trefoil factor family peptides are expressed in gastrointestinal epithelial cells and play a critical role in maintaining mucosal integrity. Although non-steroidal anti-inflammatory drugs (NSAIDs) are important causative agents of gastric mucosal lesions, few data are available about the effect of NSAIDs on trefoil family peptides in gastric mucosa.


OBJECTIVE
To examine whether indometacin, a widely used NSAID, affects trefoil factor family expression in gastric epithelial cells.


METHODS
MKN45, a cell line derived from human gastric cancer, was used. TFF1, TFF2, and TFF3 mRNA expression was assessed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). TFF2 gene transcription was also examined by luciferase reporter gene assay.


RESULTS
Relative expression level of TFF1, TFF2, TFF3 mRNA was 616: 12: 1 in unstimulated MKN45 cells. Although indometacin (1-250 micro mol/L) had no significant effect on the expression of TFF1 and TFF3 mRNA, it up-regulated TFF2 mRNA expression in a dose- and time-dependent manner. Luciferase reporter gene assay confirmed the up-regulation of TFF2 gene transcription by indometacin. Indometacin-induced up-regulation of TFF2 expression was not antagonized by externally applied prostaglandin E2.


CONCLUSIONS
These results suggest that indometacin up-regulates gastric epithelial cell TFF2 expression through a COX-independent mechanism. Since TFF peptides play an important role in gastric mucosal protection, indometacin-induced TFF2 may reduce the degree of gastric mucosal damage induced by indometacin.
Department of Gastroenterology and Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
A
A
Koitabashi
T
T
Shimada
Y
Y
Fujii
T
T
Hashimoto
K
K
Hosaka
K
K
Tabei
T
T
Namatame
M
M
Yoneda
H
H
Hiraishi
A
A
Terano
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009077:Mucins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000378:metabolism*; D000071164:Trefoil Factor-2; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; D015232:Dinoprostone; D007213:Indomethacin