{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:31:51Z","timestamp":1767706311411,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CERCA Programme\/Generalitat de Catalunya","award":["PI16\/00377","PI20\/00464","2021SGR 00521"],"award-info":[{"award-number":["PI16\/00377","PI20\/00464","2021SGR 00521"]}]},{"name":"\u201cAssociaci\u00f3 Catalana de Fibrosi Qu\u00edstica\u201d","award":["PI16\/00377","PI20\/00464","2021SGR 00521"],"award-info":[{"award-number":["PI16\/00377","PI20\/00464","2021SGR 00521"]}]},{"DOI":"10.13039\/501100004587","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (Madrid, Spain)","doi-asserted-by":"publisher","award":["PI16\/00377","PI20\/00464","2021SGR 00521"],"award-info":[{"award-number":["PI16\/00377","PI20\/00464","2021SGR 00521"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FEDER funds\/European Regional Development Fund (ERDF)","award":["PI16\/00377","PI20\/00464","2021SGR 00521"],"award-info":[{"award-number":["PI16\/00377","PI20\/00464","2021SGR 00521"]}]},{"name":"Generalitat de Catalunya","award":["PI16\/00377","PI20\/00464","2021SGR 00521"],"award-info":[{"award-number":["PI16\/00377","PI20\/00464","2021SGR 00521"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 (TNFRSF1B; TNFR2) 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-\u03b1 (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 TNFRSF1B and of other genes within the TNF pathway leading to epithelial cell death. Thus, the inhibition of the LT\u03b13-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.<\/jats:p>","DOI":"10.3390\/antiox13030368","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T10:54:38Z","timestamp":1710759278000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TNFRSF1B Signaling Blockade Protects Airway Epithelial Cells from Oxidative Stress"],"prefix":"10.3390","volume":"13","author":[{"given":"Javier","family":"Checa","sequence":"first","affiliation":[{"name":"Immune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge\u2014IDIBELL, 08908 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pau","family":"Fiol","sequence":"additional","affiliation":[{"name":"Immune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge\u2014IDIBELL, 08908 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Guevara","sequence":"additional","affiliation":[{"name":"Immune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge\u2014IDIBELL, 08908 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2827-9392","authenticated-orcid":false,"given":"Josep M.","family":"Aran","sequence":"additional","affiliation":[{"name":"Immune-Inflammatory Processes and Gene Therapeutics Group, Genes, Disease and Therapy Program, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge\u2014IDIBELL, 08908 L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1152\/physrev.00007.2018","article-title":"Structure, gating, and regulation of the CFTR anion channel","volume":"99","author":"Vergani","year":"2019","journal-title":"Physiol. 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