Abstract
Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses.
Keywords:
Cyclooxygenase-2; Egr-1; Erk1/2; Lipopolysaccharide; RAW264.7 macrophages; γ-Oryzanol.
Copyright © 2017 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Antioxidants / pharmacology*
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Cell Line
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Cyclooxygenase 2 / genetics*
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Cyclooxygenase 2 / metabolism
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Early Growth Response Protein 1 / agonists
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Early Growth Response Protein 1 / genetics*
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Early Growth Response Protein 1 / metabolism
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Gene Expression Regulation
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Genes, Reporter
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Lipopolysaccharides / pharmacology
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Luciferases / genetics
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Luciferases / metabolism
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Macrophage Activation
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Macrophages / cytology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics*
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Mitogen-Activated Protein Kinase 3 / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Phenylpropionates / pharmacology*
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Reactive Oxygen Species / antagonists & inhibitors
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Reactive Oxygen Species / metabolism
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Signal Transduction
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Transcription, Genetic
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antioxidants
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Lipopolysaccharides
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NF-kappa B
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Phenylpropionates
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Reactive Oxygen Species
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Luciferases
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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gamma-oryzanol