title: 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.affiliation: Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, No. 261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Huang
authors.forename: Shu-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Rong-Syuan
authors.initials: RS
authors.lastname: Tu
authors.forename: You-Rong
authors.initials: YR
authors.lastname: Lai
authors.forename: Chian-Jiun
authors.initials: CJ
authors.lastname: Liou
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D027845:Malus / Q000737:chemistry; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D055271:Mucin 5AC / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology*; D010695:Phlorhizin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014934:Wood / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C573420:ICAM1 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D018799:Intercellular Adhesion Molecule-1; D010695:Phlorhizin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D010693:Phloretin