General session II Moderated by Yashihiro Takami: Down-Regulation of TFF Expression by TNF-α in Gastric Epithelial Cells

Aim:  Trefoil factor family (TFF) peptides are known to facilitate wound healing in gastric mucosa. However, the regulatory mechanisms of gastric TFF expression are not fully understood yet. In this study, we examined the effect of TNF-α on TFF1 and TFF2 expression in gastric epithelial cells. Methods:  MKN45 cells were used. TFF mRNA expression was analyzed by real-time quantitative RT-PCR. Promoter sequences of TFF1 gene (−956 to +36) and TFF2 gene (−912 to +24) were inserted into pGL3 vector and reporter gene assays were performed. NF-κB activity was monitored by using a NF-κB responsive element-driven reporter vector. Results:  (1) TNF-α(0.1–30 ng/ml) down-regulated TFF1 and TFF2 mRNA expression in a dose-dependent manner. (2) Reporter gene assays also confirmed the down-regulation of TFF1 and TFF2 gene transcription by TNF-α. (3) TNF-α activated NF-κB. (4) Overexpression of dominant negative IκBα prevented both TNF-α-induced NF-κB activation and TNF-α-induced down-regulation of TFF expression. Conclusions:  TNF-α down-regulates gastric TFF expression through NF-κB pathway, suggesting that TFF expression is sensitive to inflammatory stimuli.