장기간의 안지오텐신 전환효소(ACE) 억제제의 투여가 백서 소장의 ACE에 미치는 영향과 고 프롤린식에 의한 ACE 유도에 대한 영향 및 그 유전적 조절 기전에 대한 연구

학위논문(석사)--서울대학교 대학원 :의학과 내과학전공,1997.Maste

Inhibition of C-X-C chemokines in colon cancer cells by IL-10 gene delivery using non-viral gene carrier

학위논문(박사)--서울대학교 대학원 :의학과 내과학전공,2003.Docto

Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice

Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-kappa B signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-alpha to activate NF-kappa B signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1 alpha mRNA levels in MKN-45 cells stimulated with TNF-alpha, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-alpha-induced NF-kappa B DNA binding activity. A pretreatment with TUDCA inhibited I kappa B alpha phosphorylation induced by TNF-alpha, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions: TUDCA inhibited NF-kappa B signaling in gastric epithelial cells and ameliorated ethanol-and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.N