The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro
© 2024. The Author(s)..
BACKGROUND: Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.
METHODS: We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.
RESULTS: IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.
CONCLUSION: This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Respiratory research - 25(2024), 1 vom: 28. Feb., Seite 104 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matera, Maria Gabriella [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.03.2024 Date Revised 02.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12931-024-02710-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369089383 |
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| 100 | 1 | |a Matera, Maria Gabriella |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
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| 500 | |a Date Revised 02.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features | ||
| 520 | |a METHODS: We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses | ||
| 520 | |a RESULTS: IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction | ||
| 520 | |a CONCLUSION: This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Airway epithelial cells | |
| 650 | 4 | |a Asthma | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Inhaled corticosteroid | |
| 650 | 4 | |a Long-acting muscarinic antagonists | |
| 650 | 7 | |a Muscarinic Antagonists |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Interleukin-5 |2 NLM | |
| 650 | 7 | |a Adrenal Cortex Hormones |2 NLM | |
| 650 | 7 | |a Adrenergic beta-2 Receptor Agonists |2 NLM | |
| 700 | 1 | |a Rinaldi, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Calabrese, Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a Belardo, Carmela |e verfasserin |4 aut | |
| 700 | 1 | |a Calzetta, Luigino |e verfasserin |4 aut | |
| 700 | 1 | |a Cazzola, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Page, Clive |e verfasserin |4 aut | |
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