Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells.
Reactive oxygen species (ROS) play critical roles in Helicobacter pylori (H. pylori)-associated gastric ulceration and carcinogenesis. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are involved in H. pylori-induced gastric diseases. Previously we demonstrated that H. pylori in Korean isolates induced the activation of mitogen-activated protein kinases (MAPK) and oxidant-sensitive transcription factors NF-kappaB and AP-1 which mediates the expression of iNOS and COX-2 in gastric epithelial AGS cells. beta-Carotene shows antioxidant activity and inhibits NF-kappaB-dependent gene expression in various cells. Present study aims to investigate whether beta-carotene inhibits H. pylori-induced expression of iNOS and COX-2 by suppressing the activation of MAPK, NF-kappaB, and AP-1 in gastric epithelial AGS cells. HP99 (H. pylori in Korean isolates) was added to AGS cells at the ratio of bacterium/cell, 300/1. beta-carotene inhibited H. pylori-induced increase in ROS level, the activation of MAPK (p38, the c-Jun NH2-terminal protein kinases, the extracellular signal-regulated kinases), NF-kappaB, and AP-1 and the expression of iNOS and COX-2 in AGS cells.


CONCLUSIONS
beta-carotene inhibits oxidant-mediated activation of inflammatory signaling and suppresses the expression of iNOS and COX-2 in gastric epithelial AGS cells infected with H. pylori.
Jang
S H
SH
Research Institute of Food and Nutritional Sciences, Yonsei University, Seoul, Korea.
Lim
J W
JW
Kim
H
H
D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D019207:beta Carotene / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D019207:beta Carotene; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases