{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T19:31:53Z","timestamp":1781292713031,"version":"3.54.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1\u03b1-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D3] to its active metabolite, 1\u03b1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D3, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1\u03b1-hydroxylase levels in HSNECs. Recombinant C3a was able to decrease 1\u03b1-hydroxylase and impair 25(OH)D3 to 1,25(OH)2D3 metabolism, while addition of a C3a receptor antagonist restored conversion. Conversely, 1,25(OH)2D3 suppressed Aspergillus fumigatus\u2013induced C3 and C3a levels in HSNEC supernatant. Given the ability of 1,25(OH)2D3 to modulate LL37 in other cell types, we examined its regulation in HSNECs and relationship to C3a. 1,25(OH)2D3 stimulated the secretion of LL37, whereas A. fumigatus and C3a suppressed it. Conversely, LL37 reduced the release of C3\/C3a by HSNECs. Lastly, oral steroid use and in vitro dexamethasone application both failed to increase 1\u03b1-hydroxylase or reduce C3a levels. In summary, in this article, we describe for the first time a novel relationship between complement activation and local vitamin D metabolism in airway epithelial cells. The presence of elevated C3\/C3a in patients with asthma and\/or chronic rhinosinusitis with nasal polyps may account for their impaired HSNEC 25(OH)D3 to 1,25(OH)2D3 metabolism and explain why they receive limited therapeutic benefit from oral vitamin D3 supplementation.<\/jats:p>","DOI":"10.4049\/jimmunol.2000726","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T15:14:25Z","timestamp":1657811665000},"page":"262-269","source":"Crossref","is-referenced-by-count":10,"title":["Role of C3a as a Novel Regulator of 25(OH)D3 to 1\u03b1,25-Dihydroxyvitamin D3 Metabolism in Upper Airway Epithelial Cells"],"prefix":"10.1093","volume":"209","author":[{"given":"Jennifer K","family":"Mulligan","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida , Gainesville, FL"},{"name":"Department of Otolaryngology, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-4655","authenticated-orcid":false,"given":"Dianna","family":"Nord","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeb","family":"Justice","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1533-1665","authenticated-orcid":false,"given":"Brian","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6480-0275","authenticated-orcid":false,"given":"Rodney J","family":"Schlosser","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Medical University of South Carolina , Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2025021008202901800_r1","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.jaci.2015.10.009","article-title":"Chronic rhinosinusitis pathogenesis","volume":"136","author":"Stevens","year":"2015","journal-title":"J. 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Biol."},{"key":"2025021008202901800_r30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune regulation by glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008202901800_r31","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1513\/pats.200402-018MS","article-title":"Glucocorticoids suppress inflammation but spare innate immune responses in airway epithelium","volume":"1","author":"Schleimer","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"2025021008202901800_r32","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0091-6749(97)70233-1","article-title":"Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease","volume":"100","author":"Maruo","year":"1997","journal-title":"J. Allergy Clin. 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