| Summary: | <p>Abstract</p> <p>Background</p> <p>The respiratory epithelium plays a central role in the inflammatory response in asthma and other diseases. Methoxyphenolic compounds are purported to be effective anti-inflammatory agents, but their effects on the airway epithelium have not been well characterized.</p> <p>Methods</p> <p>Human airway cells were stimulated with TNF-α in the presence or absence of 4-substituted methoxyphenols and resveratrol. The expression of various cytokines was measured by qPCR, ELISAs, and protein arrays. Reactive oxygen species (ROS) production was measured with a reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein). Activation of NF-κB was measured by nuclear translocation and phosphorylation. Ribonuclear protein association with mRNA was assessed with a biotin-RNA affinity isolation assay.</p> <p>Results</p> <p>Multiple inflammatory mediators were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF, CXCL1, CXCL10, and Serpin E1. IC<sub>50 </sub>values were obtained for each compound that showed significant anti-inflammatory activity: diapocynin (20.3 μM), resveratrol (42.7 μM), 2-methoxyhydroquinone (64.3 μM), apocynin (146.6 μM), and 4-amino-2-methoxyphenol (410 μM). The anti-inflammatory activity did not correlate with inhibition of reactive oxygen species production or NF-κB activation. However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA, indicating that they may act post-transcriptionally.</p> <p>Conclusions</p> <p>Methoxyphenols demonstrate anti-inflammatory activity in human airway cells. More potent compounds that act via similar mechanisms may have therapeutic potential as novel anti-inflammatory agents.</p>
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