Abstract
To assess the potential therapeutic properties of trans-1,3-diphenyl-2,3-epoxypropane-1-one (DPEP), its anti-inflammatory effects were investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. DPEP induced dose-dependent reduction of the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitant reduction in the production of NO and prostaglandin E(2) (PGE(2)). Additionally, DPEP suppressed the production of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. We investigated the mechanism by which DPEP inhibits NO and PGE(2) by examining the level of nuclear factor-κB (NF-κB) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signaling pathway in RAW 264.7 cells. DPEP inhibited LPS-induced phosphorylation of ERK, JNK, and p38. Furthermore, DPEP inhibited the LPS-induced phosphorylation of inhibitor κB (IκB)-α and NF-κB p50. Taken together, the results of this study demonstrate that DPEP inhibits LPS-stimulated inflammation by blocking the NF-κB and MAPK pathways in macrophages.
Copyright © 2012 Elsevier Ltd. 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 / pharmacology*
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Cell Line, Tumor
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Cyclooxygenase 2 / metabolism
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Dinoprostone / genetics
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Dinoprostone / metabolism
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Epoxy Compounds / pharmacology*
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I-kappa B Kinase / genetics
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I-kappa B Kinase / metabolism
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Inflammation / pathology
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Inflammation Mediators / antagonists & inhibitors*
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Inflammation Mediators / metabolism
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / biosynthesis
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / biosynthesis
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides / adverse effects*
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Nitric Oxide / analysis
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Phosphorylation / drug effects
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Propane / analogs & derivatives*
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Propane / pharmacology
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Signal Transduction
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents
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Epoxy Compounds
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Inflammation Mediators
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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Tumor Necrosis Factor-alpha
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trans-1,3-diphenyl-2,3-epoxypropane-1-one
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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I-kappa B Kinase
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Dinoprostone
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Propane