{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:40:51Z","timestamp":1790786451675,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["Z01 ES102005"],"award-info":[{"award-number":["Z01 ES102005"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["P50 HL073996,K23 HL144916,HL087823"],"award-info":[{"award-number":["P50 HL073996,K23 HL144916,HL087823"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM122940"],"award-info":[{"award-number":["GM122940"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,10]]},"abstract":"<jats:p>\n                    Cholesterol-25-hydroxylase (CH25H), the biosynthetic enzyme for 25-hydroxycholesterol (25HC), is most highly expressed in the lung, but its role in lung biology is poorly defined. Recently, we reported that\n                    <jats:italic>Ch25h<\/jats:italic>\n                    is induced in monocyte-derived macrophages recruited to the airspace during resolution of lung inflammation and that 25HC promotes liver X receptor\u2013dependent (LXR-dependent) clearance of apoptotic neutrophils by these cells.\n                    <jats:italic>Ch25h<\/jats:italic>\n                    and 25HC are, however, also robustly induced by lung-resident cells during the early hours of lung inflammation, suggesting additional cellular sources and targets. Here, using\n                    <jats:italic>\n                      Ch25h\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice and exogenous 25HC in lung injury models, we provide evidence that 25HC sustains proinflammatory cytokines in the airspace and augments lung injury, at least in part, by inducing LXR-independent endoplasmic reticulum stress and endothelial leak. Suggesting an autocrine effect in endothelium, inhaled LPS upregulates pulmonary endothelial\n                    <jats:italic>Ch25h<\/jats:italic>\n                    , and non-hematopoietic\n                    <jats:italic>Ch25h<\/jats:italic>\n                    deletion is sufficient to confer lung protection. In patients with acute respiratory distress syndrome, airspace 25HC and alveolar macrophage\n                    <jats:italic>CH25H<\/jats:italic>\n                    were associated with markers of microvascular leak, endothelial activation, endoplasmic reticulum stress, inflammation, and clinical severity. Taken together, our findings suggest that 25HC deriving from and acting on different cell types in the lung communicates distinct, temporal LXR-independent and -dependent signals to regulate inflammatory homeostasis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155448","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T12:02:20Z","timestamp":1677153740000},"source":"Crossref","is-referenced-by-count":21,"title":["25-Hydroxycholesterol exacerbates vascular leak during acute lung injury"],"prefix":"10.1172","volume":"8","author":[{"given":"Jennifer H.","family":"Madenspacher","sequence":"first","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9900-3604","authenticated-orcid":true,"given":"Eric 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