title: Activation of vitamin D regulates response of human bronchial epithelial cells to Aspergillus fumigatus in an autocrine fashion.
abstract: Aspergillus fumigatus (A. fumigatus) is one of the most common fungi to cause diseases in humans. Recent evidence has demonstrated that airway epithelial cells play an important role in combating A. fumigatus through inflammatory responses. Human airway epithelial cells have been proven to synthesize the active vitamin D, which plays a key role in regulating inflammation. The present study was conducted to investigate the impact of A. fumigatus infection on the activation of vitamin D and the role of vitamin D activation in A. fumigatus-elicited antifungal immunity in normal human airway epithelial cells. We found that A. fumigatus swollen conidia (SC) induced the expression of 1α-hydroxylase, the enzyme catalyzing the synthesis of active vitamin D, and vitamin D receptor (VDR) in 16HBE cells and led to increased local generation of active vitamin D. Locally activated vitamin D amplified SC-induced expression of antimicrobial peptides in 16HBE cells but attenuated SC-induced production of cytokines in an autocrine fashion. Furthermore, we identified β-glucan, the major A. fumigatus cell wall component, as the causative agent for upregulation of 1α-hydroxylase and VDR in 16HBE cells. Therefore, activation of vitamin D is inducible and provides a bidirectional regulation of the responses to A. fumigatus in 16HBE cells.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D055732:Pulmonary Aspergillosis / Q000378:metabolism; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D013172:Spores, Fungal; D014807:Vitamin D / Q000378:metabolism*; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D047071:beta-Glucans; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase