Abstract
Phloretin, a flavonoid isolated from the apple tree, is reported to have anti-inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we evaluated the suppressive effects of phloretin on intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1β-stimulated human lung epithelial A549 cells. The cells were pretreated with various concentrations of phloretin (3-100 μM), followed by induced inflammation by IL-1β. Phloretin inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM-1 gene and protein expression and suppressed monocyte adhesion to inflammatory A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. In addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both MAPK inhibitors and phloretin in inflammatory A549 cells. However, phlorizin, a derivative of phloretin, did not suppress the inflammatory response in IL-1β-stimulated A549 cells. These results suggest that phloretin might have an anti-inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1 expression via blocked NF-κB and MAPK signaling pathways.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Adhesion / drug effects
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Cell Line
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Down-Regulation / drug effects
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Humans
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Intercellular Adhesion Molecule-1 / chemistry
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism*
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / metabolism
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Lung / cytology
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Lung / drug effects*
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Lung / immunology
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Lung / metabolism
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MAP Kinase Signaling System / drug effects*
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Malus / chemistry
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Monocytes / drug effects
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Monocytes / immunology
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Mucin 5AC / agonists
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Mucin 5AC / antagonists & inhibitors
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Mucin 5AC / genetics
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Mucin 5AC / metabolism
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NF-kappa B p50 Subunit / antagonists & inhibitors
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NF-kappa B p50 Subunit / metabolism
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Phloretin / pharmacology*
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Phlorhizin / pharmacology
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Respiratory Mucosa / cytology
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Respiratory Mucosa / drug effects*
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Respiratory Mucosa / immunology
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Respiratory Mucosa / metabolism
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Wood / chemistry
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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ICAM1 protein, human
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IL1B protein, human
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Interleukin-1beta
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MUC5AC protein, human
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Mucin 5AC
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NF-kappa B p50 Subunit
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NFKB1 protein, human
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Intercellular Adhesion Molecule-1
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Phlorhizin
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Cyclooxygenase 2
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PTGS2 protein, human
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Phloretin