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Issue 10, 2014
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Sesamin suppresses macrophage-derived chemokine expression in human monocytes via epigenetic regulation

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Abstract

Background: Chemokines play important roles in the pathogenesis of asthmatic inflammation. Sesamin, a class of phytoestrogen isolated from sesame seed Sesamum indicum, is recently regarded as an anti-inflammatory agent. However, the effects of sesamin on asthma-related chemokines are unknown. To this end, we investigated the effects of sesamin on the expression interferon-γ-inducible protein-10 (IP-10/CXCL10), macrophage-derived chemokine (MDC/CCL22), growth-related oncogene-α (GRO-α/CXCL1) and tumor necrosis factor (TNF)-α in human monocytes. Methods: Cells were pretreated with sesamin before lipopolysaccharide (LPS) stimulation. IP-10, MDC, GRO-α and TNF-α were measured by ELISA. Involved receptors and intracellular signaling were investigated by receptor antagonists, pathway inhibitors, western blotting and chromatin immunoprecipitation. Results: Sesamin suppressed LPS-induced MDC in THP-1 and human primary monocytes. Sesamin suppressed LPS-induced IP-10 in THP-1 cells, but not human primary monocytes. Sesamin had no effects on LPS-induced GRO-α and TNF-α expression in THP-1 and human primary monocytes. The suppressive effect of sesamin on MDC was reversed by the estrogen receptor (ER) and peroxisomal proliferator-activated receptor (PPAR)-α antagonists. Sesamin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)-p38 and nuclear factor kappa B (NFκB)-p65. Sesamin suppressed histone H3/H4 acetylation in the MDC promoter region. Conclusion: Sesamin suppressed LPS-induced MDC expression via the ER, the PPAR-α, the MAPK-p38 pathway, the NFκB-p65 pathway and the epigenetic regulation. Sesamin may have therapeutic potential in preventing and treating asthma.

Graphical abstract: Sesamin suppresses macrophage-derived chemokine expression in human monocytes via epigenetic regulation

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Article information


Submitted
13 Apr 2014
Accepted
17 Jul 2014
First published
13 Aug 2014

Food Funct., 2014,5, 2494-2500
Article type
Paper

Sesamin suppresses macrophage-derived chemokine expression in human monocytes via epigenetic regulation

C. Hsieh, C. Kuo, H. Kuo, Y. Chen, S. Wang, D. Chao, M. Lee and C. Hung, Food Funct., 2014, 5, 2494
DOI: 10.1039/C4FO00322E

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