TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress
Progressive respiratory airway destruction due to unresolved inflammation induced by periodic infectious exacerbation episodes is a hallmark of cystic fibrosis (CF) lung pathology. To clear bacteria, neutrophils release high amounts of reactive oxygen species (ROS), which inflict collateral damage t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/3/368 |
| _version_ | 1797242256347889664 |
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| author | Javier Checa Pau Fiol Marta Guevara Josep M. Aran |
| author_facet | Javier Checa Pau Fiol Marta Guevara Josep M. Aran |
| author_sort | Javier Checa |
| collection | DOAJ |
| description | Progressive respiratory airway destruction due to unresolved inflammation induced by periodic infectious exacerbation episodes is a hallmark of cystic fibrosis (CF) lung pathology. To clear bacteria, neutrophils release high amounts of reactive oxygen species (ROS), which inflict collateral damage to the neighboring epithelial cells causing oxidative stress. A former genome-wide small interfering RNA (siRNA) screening in CF submucosal gland cells, instrumental for mucociliary clearance, proposed tumor necrosis factor receptor superfamily member 1B (<i>TNFRSF1B</i>; <i>TNFR2</i>) as a potential hit involved in oxidative stress susceptibility. Here, we demonstrate the relevance of TNFRSF1B transcript knock-down for epithelial cell protection under strong oxidative stress conditions. Moreover, a blockade of TNFR signaling through its ligand lymphotoxin-α (LTA), overexpressed in airway epithelial cells under oxidative stress conditions, using the anti-tumor necrosis factor (TNF) biologic etanercept significantly increased the viability of these cells from a toxic oxidizing agent. Furthermore, bioinformatic analyses considering our previous RNA interference (RNAi) screening output highlight the relevance of <i>TNFRSF1B</i> and of other genes within the TNF pathway leading to epithelial cell death. Thus, the inhibition of the LTα3-TNFR2 axis could represent a useful therapeutic strategy to protect the respiratory airway epithelial lining from the oxidative stress challenge because of recurrent infection/inflammation cycles faced by CF patients. |
| first_indexed | 2024-04-24T18:36:20Z |
| format | Article |
| id | doaj.art-1551d04e9e7640a99623989667709ff2 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-04-24T18:36:20Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1551d04e9e7640a99623989667709ff22024-03-27T13:18:43ZengMDPI AGAntioxidants2076-39212024-03-0113336810.3390/antiox13030368TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative StressJavier Checa0Pau Fiol1Marta Guevara2Josep M. Aran3Immune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, 08908 L’Hospitalet de Llobregat, SpainImmune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, 08908 L’Hospitalet de Llobregat, SpainImmune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, 08908 L’Hospitalet de Llobregat, SpainImmune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, 08908 L’Hospitalet de Llobregat, SpainProgressive respiratory airway destruction due to unresolved inflammation induced by periodic infectious exacerbation episodes is a hallmark of cystic fibrosis (CF) lung pathology. To clear bacteria, neutrophils release high amounts of reactive oxygen species (ROS), which inflict collateral damage to the neighboring epithelial cells causing oxidative stress. A former genome-wide small interfering RNA (siRNA) screening in CF submucosal gland cells, instrumental for mucociliary clearance, proposed tumor necrosis factor receptor superfamily member 1B (<i>TNFRSF1B</i>; <i>TNFR2</i>) as a potential hit involved in oxidative stress susceptibility. Here, we demonstrate the relevance of TNFRSF1B transcript knock-down for epithelial cell protection under strong oxidative stress conditions. Moreover, a blockade of TNFR signaling through its ligand lymphotoxin-α (LTA), overexpressed in airway epithelial cells under oxidative stress conditions, using the anti-tumor necrosis factor (TNF) biologic etanercept significantly increased the viability of these cells from a toxic oxidizing agent. Furthermore, bioinformatic analyses considering our previous RNA interference (RNAi) screening output highlight the relevance of <i>TNFRSF1B</i> and of other genes within the TNF pathway leading to epithelial cell death. Thus, the inhibition of the LTα3-TNFR2 axis could represent a useful therapeutic strategy to protect the respiratory airway epithelial lining from the oxidative stress challenge because of recurrent infection/inflammation cycles faced by CF patients.https://www.mdpi.com/2076-3921/13/3/368oxidative stressairway epithelial cellscystic fibrosisRNAi knock-downTNFRSF1B |
| spellingShingle | Javier Checa Pau Fiol Marta Guevara Josep M. Aran TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress Antioxidants oxidative stress airway epithelial cells cystic fibrosis RNAi knock-down TNFRSF1B |
| title | TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress |
| title_full | TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress |
| title_fullStr | TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress |
| title_full_unstemmed | TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress |
| title_short | TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress |
| title_sort | tnfrsf1b signaling blockade protects airway epithelial cells from oxidative stress |
| topic | oxidative stress airway epithelial cells cystic fibrosis RNAi knock-down TNFRSF1B |
| url | https://www.mdpi.com/2076-3921/13/3/368 |
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