Abstract
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.
Conclusion:
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Line
-
Cyclooxygenase 2 / genetics
-
Cyclooxygenase 2 / metabolism*
-
DNA-Binding Proteins / metabolism
-
Enzyme Activation
-
Epithelial Cells / metabolism
-
Epithelial Cells / pathology
-
Extracellular Signal-Regulated MAP Kinases / metabolism
-
Gastric Mucosa / metabolism*
-
Gastric Mucosa / microbiology
-
Gastric Mucosa / pathology
-
Gene Expression Regulation, Enzymologic*
-
Helicobacter Infections / complications
-
Helicobacter pylori / physiology*
-
Humans
-
I-kappa B Kinase / metabolism
-
Inflammation Mediators / antagonists & inhibitors*
-
Inflammation Mediators / metabolism
-
JNK Mitogen-Activated Protein Kinases / metabolism
-
NF-kappa B / metabolism
-
Nitric Oxide Synthase Type II / genetics
-
Nitric Oxide Synthase Type II / metabolism*
-
Phosphorylation
-
RNA, Messenger / metabolism
-
Reactive Oxygen Species / metabolism
-
Stomach Ulcer / enzymology
-
Stomach Ulcer / metabolism
-
Stomach Ulcer / microbiology
-
Transcription Factor AP-1 / metabolism
-
beta Carotene / pharmacology*
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
DNA-Binding Proteins
-
Inflammation Mediators
-
NF-kappa B
-
RNA, Messenger
-
Reactive Oxygen Species
-
Transcription Factor AP-1
-
beta Carotene
-
NOS2 protein, human
-
Nitric Oxide Synthase Type II
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
I-kappa B Kinase
-
Extracellular Signal-Regulated MAP Kinases
-
JNK Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases