Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 304, Issue 2, Pages G193-G202Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00103.2012
Keywords
gastric epithelial cells; nuclear factor-kappa B
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology (MEST) [2010-0008594]
- NRF of Korea Grant
- Korean Government (MEST) (MRC Program) [2010-0029507]
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Kim JM, Kim SH, Ko SH, Jung J, Chun J, Kim N, Jung HC, Kim JS. The guggulsterone derivative GG-52 inhibits NF-kappa B signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice. Am J Physiol Gastrointest Liver Physiol 304: G193-G202, 2013. First published November 1, 2012; doi:10.1152/ajpgi.00103.2012.-Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-kappa B (NF-kappa B) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-alpha in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-alpha-induced activation of I kappa B kinase (IKK) and NF-kappa B signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-kappa B activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-kappa B signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-kappa B activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.
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