{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:59:09Z","timestamp":1788832749623,"version":"build-2803163510"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"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":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18\/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells to proinflammatory cytokines alters their vitamin D metabolism, antibacterial activity, and expression of hCAP18\/LL-37. To investigate this, primary bronchial epithelial cells were differentiated at the air-liquid interface for 14 days in the presence of the proinflammatory cytokines, TNF-\u03b1 and IL-1\u03b2 (TNF-\u03b1\/IL-1\u03b2), and subsequently exposed to vitamin D (inactive 25(OH)D3 and active 1,25(OH)2D3). Expression of hCAP18\/LL-37, vitamin D receptor, and enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1) was determined using quantitative PCR, Western blot, and immunofluorescence staining. Furthermore, vitamin D\u2013mediated antibacterial activity was assessed using nontypeable Haemophilus influenzae. We found that TNF-\u03b1\/IL-1\u03b2 treatment reduced vitamin D\u2013induced expression of hCAP18\/LL-37 and killing of nontypeable H. influenzae. In addition, CYP24A1 (a vitamin D\u2013degrading enzyme) was increased by TNF-\u03b1\/IL-1\u03b2, whereas CYP27B1 (that converts 25(OH)D3 to its active form) and vitamin D receptor expression remained unaffected. Furthermore, we have demonstrated that the TNF-\u03b1\/IL-1\u03b2\u2013mediated induction of CYP24A1 was, at least in part, mediated by the transcription factor specific protein 1, and the epidermal growth factor receptor\u2013mitogen-activated protein kinase pathway. These findings indicate that TNF-\u03b1\/IL-1\u03b2 decreases vitamin D\u2013mediated antibacterial activity and hCAP18\/LL-37 expression via induction of CYP24A1 and suggest that chronic inflammation impairs protective responses induced by vitamin D.<\/jats:p>","DOI":"10.1165\/rcmb.2016-0289oc","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T15:07:58Z","timestamp":1487862478000},"page":"749-761","source":"Crossref","is-referenced-by-count":38,"title":["Proinflammatory Cytokines Impair Vitamin D\u2013Induced Host Defense in Cultured Airway Epithelial Cells"],"prefix":"10.1093","volume":"56","author":[{"given":"Jasmijn A.","family":"Schrumpf","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gimano D.","family":"Amatngalim","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, 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