Phloretin, an Apple Polyphenol, Inhibits Pathogen‐Induced Mucin Overproduction
| Autor: | Yuanpu Peter Di, Kiflai Bein, Aaron Barchowsky, Natalya Bondarchuk, George D. Leikauf, Rahel L. Birru, Heather Wells |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Haemophilus Infections Phloretin Moraxellaceae Infections Mice Inbred Strains Mucin 5AC Article Cell Line Microbiology 03 medical and health sciences chemistry.chemical_compound Epidermal growth factor Animals Humans Pseudomonas Infections Secretion Protein kinase A 030109 nutrition & dietetics Chemistry Mucin technology industry and agriculture Epithelial Cells respiratory system Mucus 030104 developmental biology Malus Dietary Supplements Host-Pathogen Interactions TLR4 Female Reactive Oxygen Species Food Science Biotechnology |
| Zdroj: | Mol Nutr Food Res |
| ISSN: | 1613-4133 1613-4125 |
| DOI: | 10.1002/mnfr.202000658 |
| Popis: | Scope Bacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. We examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases. Methods and results We analyzed expression of the mucus constituent mucin 5AC (MUC5AC) in FVB/NJ mice and NCI-H292 epithelial cells. Nontypeable Haemophilus influenzae (NTHi)-infected mice developed increased MUC5AC mRNA, which a diet containing phloretin inhibited. In NCI-H292 cells, NTHi, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa increased MUC5AC mRNA, which phloretin inhibited. Phloretin also diminished NTHi-induced MUC5AC protein secretion. NTHi-induced increased MUC5AC required toll-like receptor 4 (TLR4) and NADH oxidase 4 (NOX4) signaling and subsequent activation of the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Phloretin inhibited NTHi-induced TLR4/NOX4 and EGFR/MAPK signaling, thereby preventing increased MUC5AC mRNA. EGFR activation can also result from increased EGFR ligand synthesis and subsequent ligand activation by matrix metalloproteinases (MMPs). In NCI-H292 cells, NTHi increased EGFR ligand and MMP1 and MMP13 mRNA, which phloretin inhibited. Conclusions In summary, phloretin is a promising therapeutic candidate for preventing bacterial-induced mucus overproduction. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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