{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:35:08Z","timestamp":1791668108976,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1449 \u2010 431232613 Z02"],"award-info":[{"award-number":["CRC 1449 \u2010 431232613 Z02"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mucus plugging and non\u2010resolving inflammation are inherent features of cystic fibrosis (CF) that may lead to progressive lung disease and exercise intolerance, which are the main causes of morbidity and mortality for people with CF. Therefore, understanding the influence of mucus on basic mechanisms underlying the inflammatory response and identifying strategies to resolve mucus\u2010driven airway inflammation and consequent morbidity in CF are of wide interest. Here, we investigated the effects of the proresolving lipid mediator resolvin (Rv) D1 on mucus\u2010related inflammation as a proof\u2010of\u2010concept to alleviate the burden of lung disease and restore exercise intolerance in CF. We tested the effects of RvD1 on inflammatory responses of human organotypic airways and leukocytes to CF mucus and of humanized mice expressing the epithelial Na\u2009+\u2009channel (\u03b2ENaC\u2010Tg) having CF\u2010like mucus obstruction, lung disease, and physical exercise intolerance. RvD1 reduced pathogenic phenotypes of CF\u2010airway supernatant (ASN)\u2010stimulated human neutrophils, including loss of L\u2010selectin shedding and CD16. RNASeq analysis identified select transcripts and pathways regulated by RvD1 in ASN\u2010stimulated CF bronchial epithelial cells that are involved in sugar metabolism, NF\u2010\u03baB activation and inflammation, and response to stress. In in vivo inflammation using \u03b2ENaC TG mice, RvD1 reduced total leukocytes, PMN, and interstitial Siglec\u2010M\u03a6 when given at 6\u20138\u2009weeks of age, and in older mice at 10\u201312\u2009weeks of age, along with the decrease of pro\u2010inflammatory chemokines and increase of anti\u2010inflammatory IL\u201010. Furthermore, RvD1 treatment promoted the resolution of pulmonary exacerbation caused by\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infection and significantly enhanced physical activity and energy expenditure associated with mucus obstruction, which was impaired in \u03b2ENaC\u2010Tg mice compared with wild\u2010type. These results demonstrate that RvD1 can rectify features of CF and offer proof\u2010of\u2010concept for its therapeutic application in this and other muco\u2010obstructive lung diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301495r","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T04:10:38Z","timestamp":1697083838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Resolvin\n                    <scp>D1<\/scp>\n                    improves airway inflammation and exercise capacity in cystic fibrosis lung disease"],"prefix":"10.1096","volume":"37","author":[{"given":"Giulia","family":"Ferri","sequence":"first","affiliation":[{"name":"Department of Medical, Oral and Biotechnology Sciences University of Chieti\u2010Pescara  Chieti 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