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- Title
Indometacin up-regulates TFF2 expression in gastric epithelial cells.
- Authors
Koitabashi, A.; Shimada, T.; Fujii, Y.; Hashimoto, T.; Hosaka, K.; Tabei, K.; Namatame, T.; Yoneda, M.; Hiraishi, H.; Terano, A.
- Abstract
: 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. : To examine whether indometacin, a widely used NSAID, affects trefoil factor family expression in gastric epithelial cells. : 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. : Relative expression level of TFF1, TFF2, TFF3 mRNA was 616: 12: 1 in unstimulated MKN45 cells. Although indometacin (1–250 µmol / 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. : 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.
- Subjects
PEPTIDES; GASTROINTESTINAL system; EPITHELIAL cells; MUCOUS membranes; GENETIC transcription; PROTEINS
- Publication
Alimentary Pharmacology & Therapeutics, 2004, Vol 20, p171
- ISSN
0269-2813
- Publication type
Article
- DOI
10.1111/j.1365-2036.2004.01991.x