{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:33:20Z","timestamp":1787020400297,"version":"build-2736575974"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"KUL","award":["C24\/15\/30"],"award-info":[{"award-number":["C24\/15\/30"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied vitamin D sufficient (VDS) or deficient (VDD) mice in whom 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      (0.2\u00a0\u03bcg\/kg) or a vehicle followed by lipopolysaccharide (LPS 25\u00a0\u00b5g) were delivered to the lung as a micro-spray.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Local 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      reduced LPS-induced inflammatory cells in bronchoalveolar lavage (BAL) in VDS (absolute number of cells: \u2212\u200957% and neutrophils \u2212\u200951% p\u2009&lt;\u20090.01) and tended to diminish LPS-increased CXCL5 BAL levels in VDS (\u2212\u200940%, p\u2009=\u20090.05) while it had no effect on CXCL1 and CXCL2 in BAL and mRNA in lung of VDS and VDD. It also significantly attenuated the increased IL-13 in BAL and lung, especially in VDD mice (\u2212\u200941 and \u2212\u200975%, respectively). mRNA expression of Claudin-18 in lung was significantly lower in VDS mice with local 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      while Claudin-3, -5 and -8 mRNA levels remained unchanged. Finally, in VDD mice only, LPS reduced lung mRNA expression of adhesion junction Zona-occludens-1, in addition to increasing uric acid and total protein in BAL, which both were prevented by local 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Under normal levels of vitamin D, local 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      nebulization into the lung efficiently reduced LPS induction of inflammatory cells in BAL and slightly attenuated LPS-increase in CXCL5. In case of severe vitamin D deficiency, although local 1\u03b1,25(OH)\n                      <jats:sub>2<\/jats:sub>\n                      D\n                      <jats:sub>3<\/jats:sub>\n                      nebulization failed to significantly minimize cellular inflammation in BAL at this dose, it prevented epithelial barrier leakage and damage in lung. Additional research is needed to determine the potential long-term beneficial effects of local 1\u03b1,25(OH)2D3 nebulization on lung inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-022-01997-9","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:04:41Z","timestamp":1648587881000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Local nebulization of 1\u03b1,25(OH)2D3 attenuates LPS-induced acute lung inflammation"],"prefix":"10.1186","volume":"23","author":[{"given":"Jef","family":"Serr\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolien","family":"Mathyssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Tanjeko","family":"Ajime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Heigl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Verlinden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Verstuyf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Cataldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Vanoirbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Vanaudenaerde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-7437","authenticated-orcid":false,"given":"Ghislaine","family":"Gayan-Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"1997_CR1","unstructured":"2020 Gold Reports. 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The authors confirm that the work described has not been published previously, is not under consideration for publication elsewhere, and its publication has been approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form in English or in any other language, without the written consent of the copyright holder.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"76"}}