Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells.

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.

• Authors: Wen-Chung Huang, Shu-Ju Wu, Rong-Syuan Tu, You-Rong Lai, Chian-Jiun Liou
• Journal: Food & function (Food Funct) Vol. 6 Issue 6 Pg. 1960-7 (Jun 2015) ISSN: 2042-650X [Electronic] England
• PMID: 25996641 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• ICAM1 protein, human
• IL1B protein, human
• Interleukin-1beta
• MUC5AC protein, human
• Mucin 5AC
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• Intercellular Adhesion Molecule-1
• Phlorhizin
• Cyclooxygenase 2
• PTGS2 protein, human
• Phloretin

Topics

• Active Transport, Cell Nucleus (drug effects)
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line
• Cyclooxygenase 2 (chemistry, genetics, metabolism)
• Down-Regulation (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (chemistry, genetics, metabolism)
• Interleukin-1beta (antagonists & inhibitors, metabolism)
• Lung (cytology, drug effects, immunology, metabolism)
• MAP Kinase Signaling System (drug effects)
• Malus (chemistry)
• Monocytes (drug effects, immunology)
• Mucin 5AC (agonists, antagonists & inhibitors, genetics, metabolism)
• NF-kappa B p50 Subunit (antagonists & inhibitors, metabolism)
• Phloretin (pharmacology)
• Phlorhizin (pharmacology)
• Phosphorylation (drug effects)
• Protein Processing, Post-Translational (drug effects)
• Respiratory Mucosa (cytology, drug effects, immunology, metabolism)
• Wood (chemistry)