Abstract | BACKGROUND: METHODS: Primary human nasal (HNE) and tracheal (HTE) epithelial cell cultures were infected with HCoV-229E. RESULTS: Pretreatment of HNE and HTE cells with glycopyrronium or formoterol decreased viral RNA levels and/or titers, the expression of the HCoV-229E receptor CD13, the number and fluorescence intensity of acidic endosomes where HCoV-229E RNA enters the cytoplasm, and the infection-induced production of cytokines, including IL-6, IL-8, and IFN-β. Treatment of the cells with the CD13 inhibitor 2'2'-dipyridyl decreased viral titers. Pretreatment of the cells with a combination of three drugs ( glycopyrronium, formoterol, and budesonide) exerted additive inhibitory effects on viral titers and cytokine production. Pretreatment of HNE cells with glycopyrronium or formoterol reduced the susceptibility to infection, and pretreatment with the three drugs inhibited activation of nuclear factor-kappa B p50 and p65 proteins. Pretreatment with formoterol increased cAMP levels and treatment with cAMP decreased viral titers, CD13 expression, and the fluorescence intensity of acidic endosomes. CONCLUSIONS:
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Authors | Mutsuo Yamaya, Hidekazu Nishimura, Xue Deng, Mitsuru Sugawara, Oshi Watanabe, Kazuhiro Nomura, Yoshitaka Shimotai, Haruki Momma, Masakazu Ichinose, Tetsuaki Kawase |
Journal | Respiratory investigation
(Respir Investig)
Vol. 58
Issue 3
Pg. 155-168
(May 2020)
ISSN: 2212-5353 [Electronic] Netherlands |
PMID | 32094077
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Adrenergic beta-2 Receptor Agonists
- Cytokines
- Muscarinic Antagonists
- Budesonide
- CD13 Antigens
- Glycopyrrolate
- Formoterol Fumarate
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Topics |
- Adrenergic beta-2 Receptor Agonists
(pharmacology)
- Budesonide
(pharmacology)
- CD13 Antigens
(metabolism)
- Cells, Cultured
- Coronavirus
(physiology)
- Cytokines
(metabolism)
- Epithelial Cells
(metabolism, virology)
- Formoterol Fumarate
(pharmacology)
- Glycopyrrolate
(pharmacology)
- Humans
- Muscarinic Antagonists
(pharmacology)
- Nasal Mucosa
(cytology)
- Trachea
(cytology)
- Virus Replication
(drug effects)
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