{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:49:24Z","timestamp":1793386164357,"version":"4.5.0"},"reference-count":18,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"abstract":"<jats:p>Introduction: Interleukin-41 (IL-41), also known as Metrnl, is a multifunctional adipokine recognized for its neurotrophic and anti-inflammatory properties that play a significant role in diseases such as sepsis and chronic obstructive pulmonary disease. Despite its crucial biological functions, the mechanisms by which IL-41 mitigates lipopolysaccharide (LPS)-induced acute lung injury (ALI) are not well understood. This study aimed to elucidate the protective effects of IL-41 against LPS-induced inflammation and apoptosis in a murine model and in vitro using bronchial epithelial cells (Beas-2b). Methods: We administered recombinant IL-41 to mice subjected to LPS-induced ALI and observed changes in lung histopathology, inflammation, and apoptosis. Concurrently, Beas-2b cells were transfected with IL-41 constructs, and the role of the AMPK\/SIRT1 pathway was investigated using specific inhibitors and agonists. Results: Our results demonstrated that LPS-induced ALI is characterized by increased inflammatory cell chemotaxis in lung lavage fluid, enhanced phosphorylation of NF\u03baB p65, and elevated Bax protein expression, coupled with a decrease in IL-41 protein levels. Treatment with recombinant IL-41 effectively mitigated these pathological changes by upregulating AMPK phosphorylation and SIRT1 expression and inhibiting I\u03baB\/NF\u03baB p65 phosphorylation. In cellular assays, overexpression of IL-41 reversed LPS-induced oxidative stress, apoptosis, and the secretion of inflammatory cytokines, whereas suppression of IL-41 or inhibition of AMPK reversed these protective effects. Conclusions: In conclusion, IL-41 exerts significant protective effects against ALI by activating the AMPK\/SIRT1 signaling pathway and reducing excessive inflammation and apoptosis. These findings suggest that IL-41 holds promise as a therapeutic target for ALI, potentially allowing for personalized treatments based on serum IL-41 levels. <\/jats:p>","DOI":"10.1159\/000542112","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T17:01:19Z","timestamp":1732294879000},"page":"1-12","source":"Crossref","is-referenced-by-count":1,"title":["Metrnl\/IL-41 Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Inflammatory Responses through the AMPK\/SIRT1 Signaling Pathway"],"prefix":"10.1159","author":[{"given":"Guannan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpsurg.2020.100777"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0519-RA"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-020-00327-4"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2021.01.007"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15301"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2016.1086752"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-68483-3_4"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00179"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-018-0045-3"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.969422"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106197"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.419"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.10.048"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00714-6"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00803-8"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.199"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109690"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/iaa\/article-pdf\/doi\/10.1159\/000542112\/4303733\/000542112.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/iaa\/article-pdf\/doi\/10.1159\/000542112\/4303733\/000542112.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T14:56:42Z","timestamp":1745420202000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000542112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":18,"URL":"https:\/\/doi.org\/10.1159\/000542112","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]}}}