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Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-κB and MAPK Signaling in Interleukin-1β-Stimulated Human Lung Epithelial Cells

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Abstract

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-1β-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3–100 μM) followed by treatment with IL-1β 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-κB), 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 PGE2, COX-2, TNF-α, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1β-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-κB. 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-κB and MAPK signaling pathways.

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Funding

This study was supported in part by grants from the Chang Gung Memorial Hospital (CMRPF1G0201), the Ministry of Science and Technology in Taiwan (MOST 105-2320-B-255-004), and Chang Gung University of Science and Technology (EZRPF3FG0071).

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Wen-Chung Huang and Ling-Yu Wu designed the study and performed the experiments. Sindy Hu searched the literature and performed the experiments. Shu-Ju analyzed interpretation of data and drafting the manuscript.

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Correspondence to Shu-Ju Wu.

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The authors declare that they have no conflict of interest.

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Huang, WC., Wu, LY., Hu, S. et al. Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-κB and MAPK Signaling in Interleukin-1β-Stimulated Human Lung Epithelial Cells. Inflammation 41, 1934–1944 (2018). https://doi.org/10.1007/s10753-018-0837-0

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