PMID- 29758489 OWN - NLM STAT- MEDLINE DCOM- 20181012 LR - 20211204 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 60 DP - 2018 Jul TI - Fisetin inhibits the generation of inflammatory mediators in interleukin-1beta-induced human lung epithelial cells by suppressing the NF-kappaB and ERK1/2 pathways. PG - 202-210 LID - S1567-5769(18)30215-7 [pii] LID - 10.1016/j.intimp.2018.05.004 [doi] AB - Fisetin, a flavone that can be isolated from fruits and vegetables, has anti-tumor and anti-oxidative properties and ameliorates airway hyperresponsiveness in asthmatic mice. This study investigated whether fisetin can suppress the expression of inflammatory mediators and intercellular adhesion molecule 1 (ICAM-1) in A549 human lung epithelial cells that were stimulated with interleukin-1beta (IL-1beta) to induce inflammatory responses. A549 cells were treated with fisetin (3-30 muM) and then with IL-1beta. Fisetin significantly inhibited COX-2 expression and reduced prostaglandin E(2) production, and it suppressed the levels of IL-8, CCL5, monocyte chemotactic protein 1, tumor necrosis factor alpha, and IL-6. Fisetin also significantly attenuated the expression of chemokine and inflammatory cytokine genes and decreased the expression of ICAM-1, which mediates THP-1 monocyte adhesion to inflammatory A549 cells. Fisetin decreased the translocation of nuclear transcription factor kappa-B (NF-kappaB) subunit p65 into the nucleus and inhibited the phosphorylation of proteins in the ERK1/2 pathway. Co-treatment of IL-1beta-stimulated A549 cells with ERK1/2 inhibitors plus fisetin reduced ICAM-1 expression. Furthermore, fisetin significantly increased the effects of the protective antioxidant pathway by promoting the expression of nuclear factor erythroid-2-related factor-2 and heme oxygenase 1. Taken together, these data suggest that fisetin has anti-inflammatory effects and that it suppresses the expression of chemokines, inflammatory cytokines, and ICAM-1 by suppressing the NF-kappaB and ERK1/2 signaling pathways in IL-1beta-stimulated human lung epithelial A549 cells. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Peng, Hui-Ling AU - Peng HL AD - Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan. FAU - Huang, Wen-Chung AU - Huang WC AD - Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan. Electronic address: wchuang@mail.cgust.edu.tw. FAU - Cheng, Shu-Chen AU - Cheng SC AD - Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Liou, Chian-Jiun AU - Liou CJ AD - Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan; Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan. Electronic address: ccliu@mail.cgust.edu.tw. LA - eng PT - Journal Article DEP - 20180512 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Flavonoids) RN - 0 (Flavonols) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (NFE2L2 protein, human) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - OO2ABO9578 (fisetin) SB - IM MH - A549 Cells MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Line MH - Cyclooxygenase 2/genetics/metabolism MH - Cytokines/*metabolism MH - Epithelial Cells/*drug effects/metabolism MH - Flavonoids/*pharmacology MH - Flavonols MH - Heme Oxygenase-1/metabolism MH - Humans MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Lung/cytology MH - MAP Kinase Signaling System/*drug effects MH - NF-E2-Related Factor 2/metabolism MH - NF-kappa B/*antagonists & inhibitors/metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - Anti-inflammation OT - COX-2 OT - ERK1/2 OT - Fisetin OT - ICAM-1 OT - NF-kappaB EDAT- 2018/05/15 06:00 MHDA- 2018/10/13 06:00 CRDT- 2018/05/15 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/05/04 00:00 [revised] PHST- 2018/05/08 00:00 [accepted] PHST- 2018/05/15 06:00 [pubmed] PHST- 2018/10/13 06:00 [medline] PHST- 2018/05/15 06:00 [entrez] AID - S1567-5769(18)30215-7 [pii] AID - 10.1016/j.intimp.2018.05.004 [doi] PST - ppublish SO - Int Immunopharmacol. 2018 Jul;60:202-210. doi: 10.1016/j.intimp.2018.05.004. Epub 2018 May 12.