Proinflammatory Cytokines Impair Vitamin D- Induced Host Defense in Cultured Airway Epithelial Cells
| Autor: | Schrumpf, Jasmijn A, Amatngalim, Gimano D, Veldkamp, Joris B, Verhoosel, Renate M, Ninaber, Dennis K, Ordonez Alvarez, Soledad, van der Does, Anne M, Haagsman, Henk P, Hiemstra, Pieter S, LS Moleculaire Afweer, Infection & Immunity, dI&I I&I-3 |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Time Factors Clinical Biochemistry Interleukin-1beta vitamin D Calcitriol receptor chemistry.chemical_compound Epidermal growth factor Extracellular Signal-Regulated MAP Kinases Vitamin D3 24-Hydroxylase Cells Cultured Interleukin-17 Cell Differentiation ErbB Receptors host defense Cytokines medicine.symptom Inflammation Mediators Pulmonary and Respiratory Medicine Vitamin medicine.medical_specialty Sp1 Transcription Factor proinflammatory mediators Acute Lung Injury Inflammation Bronchi Biology vitamin D deficiency Proinflammatory cytokine 03 medical and health sciences CYP24A1 Cathelicidins Internal medicine medicine Vitamin D and neurology Humans Molecular Biology Calcifediol hCAP18/LL-37 Microbial Viability Tumor Necrosis Factor-alpha Mucins Epithelial Cells Cell Biology medicine.disease Haemophilus influenzae 030104 developmental biology Endocrinology chemistry airway epithelial cells Antimicrobial Cationic Peptides |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology, 692. American Thoracic Society STARTPAGE=692;ISSN=1044-1549;TITLE=American Journal of Respiratory Cell and Molecular Biology American Journal of Respiratory Cell and Molecular Biology, 56(6), 749-761 |
| ISSN: | 1044-1549 |
| Popis: | 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-α and IL-1β (TNF-α/IL-1β), 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-mediated antibacterial activity was assessed using nontypeable Haemophilus influenzae. We found that TNF-α/IL-1β treatment reduced vitamin D-induced expression of hCAP18/LL-37 and killing of nontypeable H. influenzae. In addition, CYP24A1 (a vitamin D-degrading enzyme) was increased by TNF-α/IL-1β, 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-α/IL-1β-mediated induction of CYP24A1 was, at least in part, mediated by the transcription factor specific protein 1, and the epidermal growth factor receptor-mitogen-activated protein kinase pathway. These findings indicate that TNF-α/IL-1β decreases vitamin D-mediated antibacterial activity and hCAP18/LL-37 expression via induction of CYP24A1 and suggest that chronic inflammation impairs protective responses induced by vitamin D. |
| Databáze: | OpenAIRE |
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