PMID- 29959625 OWN - NLM STAT- MEDLINE DCOM- 20190109 LR - 20190109 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 41 IP - 5 DP - 2018 Oct TI - Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-kappaB and MAPK Signaling in Interleukin-1beta-Stimulated Human Lung Epithelial Cells. PG - 1934-1944 LID - 10.1007/s10753-018-0837-0 [doi] AB - Spilanthol a phytochemical derived from the Spilanthes acmella plant has antimicrobial, antioxidant, and anti-inflammatory properties. This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1beta-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3-100 muM) followed by treatment with IL-1beta to induce inflammation. The protein levels of pro-inflammatory cytokines, chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-kappaB), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. Spilanthol decreased the expression of PGE(2), COX-2, TNF-alpha, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1beta-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-kappaB. These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-kappaB and MAPK signaling pathways. Graphical Abstract ᅟ. FAU - Huang, Wen-Chung AU - Huang WC AD - Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology, 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, 33303, Taiwan. AD - Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan, 33303, Taiwan. FAU - Wu, Ling-Yu AU - Wu LY AD - Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and 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, 33303, Taiwan. FAU - Hu, Sindy AU - Hu S AD - Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan, 33303, Taiwan. AD - Department of Cosmetic Science, Research Center for Food and Cosmetic Safety, and 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, 33303, Taiwan. FAU - Wu, Shu-Ju AU - Wu SJ AD - Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology, 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, 33303, Taiwan. sjwu@gw.cgust.edu.tw. AD - Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and 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, 33303, Taiwan. sjwu@gw.cgust.edu.tw. AD - Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Guishan Dist., Taoyuan, 33303, Taiwan. sjwu@gw.cgust.edu.tw. LA - eng GR - MOST 105-2320-B-255-004/Ministry of Science and Technology in Taiwan/ GR - EZRPF3FG0071/Chang Gung University of Science and Technology/ GR - CMRPF1G0201/Chang Gung Memorial Hospital, Linkou/ PT - Journal Article PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (N-isobutyl-2E-decenamide) RN - 0 (NF-kappa B) RN - 0 (Polyunsaturated Alkamides) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - A549 Cells MH - Anti-Inflammatory Agents/pharmacology MH - Cyclooxygenase 2/drug effects/*metabolism MH - Epithelial Cells/*metabolism MH - Humans MH - Inflammation Mediators/metabolism MH - Intercellular Adhesion Molecule-1/drug effects/*metabolism MH - Interleukin-1beta/pharmacology MH - Mitogen-Activated Protein Kinases/*antagonists & inhibitors MH - NF-kappa B/*antagonists & inhibitors MH - Phosphorylation/drug effects MH - Polyunsaturated Alkamides/*pharmacology MH - Signal Transduction/*drug effects OTO - NOTNLM OT - ICAM-1 OT - MAPK OT - NF-kappaB OT - chemokines OT - spilanthol EDAT- 2018/07/01 06:00 MHDA- 2019/01/10 06:00 CRDT- 2018/07/01 06:00 PHST- 2018/07/01 06:00 [pubmed] PHST- 2019/01/10 06:00 [medline] PHST- 2018/07/01 06:00 [entrez] AID - 10.1007/s10753-018-0837-0 [pii] AID - 10.1007/s10753-018-0837-0 [doi] PST - ppublish SO - Inflammation. 2018 Oct;41(5):1934-1944. doi: 10.1007/s10753-018-0837-0.