The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro
Abstract 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 rest...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-024-02710-8 |
| _version_ | 1797273506751184896 |
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| author | Maria Gabriella Matera Barbara Rinaldi Cecilia Calabrese Carmela Belardo Luigino Calzetta Mario Cazzola Clive Page |
| author_facet | Maria Gabriella Matera Barbara Rinaldi Cecilia Calabrese Carmela Belardo Luigino Calzetta Mario Cazzola Clive Page |
| author_sort | Maria Gabriella Matera |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T14:44:20Z |
| format | Article |
| id | doaj.art-10bb2828b54c4c25a28aae842e455bec |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-07T14:44:20Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-10bb2828b54c4c25a28aae842e455bec2024-03-05T20:02:41ZengBMCRespiratory Research1465-993X2024-02-012511810.1186/s12931-024-02710-8The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitroMaria Gabriella Matera0Barbara Rinaldi1Cecilia Calabrese2Carmela Belardo3Luigino Calzetta4Mario Cazzola5Clive Page6Unit of Pharmacology, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Unit of Pharmacology, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”Unit of Pharmacology, Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of ParmaUnit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”Pulmonary Pharmacology Unit, Institute of Pharmaceutical Science, King’s CollegeAbstract 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.https://doi.org/10.1186/s12931-024-02710-8Airway epithelial cellsAsthmaInhaled corticosteroidInflammationLong-acting muscarinic antagonists |
| spellingShingle | Maria Gabriella Matera Barbara Rinaldi Cecilia Calabrese Carmela Belardo Luigino Calzetta Mario Cazzola Clive Page The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro Respiratory Research Airway epithelial cells Asthma Inhaled corticosteroid Inflammation Long-acting muscarinic antagonists |
| title | The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
| title_full | The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
| title_fullStr | The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
| title_full_unstemmed | The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
| title_short | The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro |
| title_sort | effect of combining an inhaled corticosteroid and a long acting muscarinic antagonist on human airway epithelial cells in vitro |
| topic | Airway epithelial cells Asthma Inhaled corticosteroid Inflammation Long-acting muscarinic antagonists |
| url | https://doi.org/10.1186/s12931-024-02710-8 |
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