Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ∼20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better unders...

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Bibliographic Details
Published in:The Journal of biological chemistry 2017-05, Vol.292 (20), p.8484-8497
Main Authors: Hariri, Benjamin M., McMahon, Derek B., Chen, Bei, Freund, Jenna R., Mansfield, Corrine J., Doghramji, Laurel J., Adappa, Nithin D., Palmer, James N., Kennedy, David W., Reed, Danielle R., Jiang, Peihua, Lee, Robert J.
Format: Article
Language:English
Subjects:
A549 Cells
airway surface liquid
Anti-Inflammatory Agents - pharmacology
antimicrobial peptide (AMP)
bitter taste receptor
chronic rhinosinusitis
Flavones - pharmacology
flavonoid
Humans
Immunity, Innate - drug effects
Immunity, Innate - genetics
Immunology
innate immunity
Mucin 5AC - genetics
Mucin 5AC - immunology
mucociliary clearance
Nasal Mucosa - immunology
nitric oxide
Nitric Oxide - genetics
Nitric Oxide - immunology
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type II - immunology
Polymorphism, Genetic
polyphenol
protein kinase C (PKC)
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - immunology
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Summary:Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ∼20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potentially important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and inducible NOS up-regulation as well as cytokine release in primary and cultured airway cells in response to several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.771949