Inhibitory effect of butein on tumor necrosis factor-α-induced expression             of cell adhesion molecules in human lung epithelial cells via inhibition of reactive             oxygen species generation, NF-κB activation and Akt phosphorylation.
Cell adhesion molecules play an important role in inflammatory response,             angiogenesis and tumor progression. Butein (tetrahydroxychalcone) is a small molecule             from natural sources, known to be a potential therapeutic drug with anti-inflammatory,             anticancer and antioxidant activities. In the present study, we investigated the             inhibitory effect of butein on tumor necrosis factor (TNF)-α-induced adhesion             molecule expression and its molecular mechanism of action. Butein significantly             decreased TNF-α-induced monocyte (U937) cell adhesion to lung epithelial cells             in a dose-dependent manner. Butein also inhibited the protein and mRNA expression             of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion             molecule-1 (VCAM-1) in TNF-α-stimulated A549 human lung epithelial cells in a             dose-dependent manner. Butein inhibited TNF-α-induced reactive oxygen species             (ROS) generation and nuclear factor-κB (NF-κB) activation in A549 cells; it also             inhibited the phosphorylation of MAPKs and Akt, suggesting that the MAPK/Akt signaling             pathway may be involved in the butein-mediated inhibition of TNF-α-induced leukocyte             adhesion to A549 cells. Collectively, our results suggest that butein affects             cell adhesion through the inhibition of TNF-α-induced ICAM-1 and VCAM-1 expression             by inhibiting the NF-κB/MAPK/Akt signaling pathway and ROS generation, thereby,             elucidating the role of butein in the anti-inflammatory response.
Department of Immunology, School of Medicine, Keimyung University,                     Daegu, Republic of Korea.
Ji Hoon
JH
Jang
Eun Sun
ES
Yang
Kyoung-Jin
KJ
Min
Taeg Kyu
TK
Kwon
D000111:Acetylcysteine / Q000494:pharmacology; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D047188:Chalcones / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D047188:Chalcones; D002839:Chromans; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C485184:enhanced green fluorescent protein; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; C040918:butein; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine