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-κB signaling in gastric epithelial cells. Moreover, th...

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Main Authors: Su Hwan Kim, Ji Won Kim, Seong-Joon Koh, Sang Gyun Kim, Jeong Mo Bae, Jung Ho Kim, Jeong Hwan Park, Kee Don Choi, Hyoun Woo Kang, Byeong Gwan Kim, Kook Lae Lee
Format: Article
Language:English
Published: Jin Publishing & Printing Co. 2022-04-01
Series:The Korean Journal of Gastroenterology
Subjects:
Online Access:https://www.kjg.or.kr/journal/view.html?uid=5809&vmd=Full
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author Su Hwan Kim
Ji Won Kim
Seong-Joon Koh
Sang Gyun Kim
Jeong Mo Bae
Jung Ho Kim
Jeong Hwan Park
Kee Don Choi
Hyoun Woo Kang
Byeong Gwan Kim
Kook Lae Lee
author_facet Su Hwan Kim
Ji Won Kim
Seong-Joon Koh
Sang Gyun Kim
Jeong Mo Bae
Jung Ho Kim
Jeong Hwan Park
Kee Don Choi
Hyoun Woo Kang
Byeong Gwan Kim
Kook Lae Lee
author_sort Su Hwan Kim
collection DOAJ
description 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-κB 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)-α to activate NF-κB 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-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, 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-κB 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.
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spelling doaj.art-6d237c22fbff4d899de5ae41ff9b02362023-09-27T02:33:33ZengJin Publishing & Printing Co.The Korean Journal of Gastroenterology1598-99922233-68692022-04-0179416116910.4166/kjg.2022.003Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in MiceSu Hwan Kim0Ji Won Kim1https://orcid.org/0000-0002-1214-5544Seong-Joon Koh2Sang Gyun Kim3Jeong Mo Bae4Jung Ho Kim5Jeong Hwan Park6Kee Don Choi7Hyoun Woo Kang8Byeong Gwan Kim 9Kook Lae Lee10Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, KoreaDepartment of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, KoreaDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaSeoul National University College of Medicine; Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Pathology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, KoreaDepartment of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaDepartment of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, KoreaDepartment of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, KoreaBackground/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-κB 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)-α to activate NF-κB 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-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, 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-κB 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.https://www.kjg.or.kr/journal/view.html?uid=5809&vmd=Fullgastritisethanolanti-inflammatory agentsnon-steroidalmiceursodoxicoltaurine
spellingShingle Su Hwan Kim
Ji Won Kim
Seong-Joon Koh
Sang Gyun Kim
Jeong Mo Bae
Jung Ho Kim
Jeong Hwan Park
Kee Don Choi
Hyoun Woo Kang
Byeong Gwan Kim
Kook Lae Lee
Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
The Korean Journal of Gastroenterology
gastritis
ethanol
anti-inflammatory agents
non-steroidal
mice
ursodoxicoltaurine
title Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
title_full Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
title_fullStr Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
title_full_unstemmed Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
title_short Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice
title_sort tauroursodeoxycholic acid inhibits nuclear factor kappa b signaling in gastric epithelial cells and ameliorates gastric mucosal damage in mice
topic gastritis
ethanol
anti-inflammatory agents
non-steroidal
mice
ursodoxicoltaurine
url https://www.kjg.or.kr/journal/view.html?uid=5809&vmd=Full
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