title: 1,25(OH)2D3 and VDR Signaling Pathways Regulate the Inhibition of Dectin-1 Caused by Cyclosporine A in Response to Aspergillus Fumigatus in Human Corneal Epithelial Cells.
abstract: BACKGROUND
  The objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition.
  
  
  METHODS
  Immortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A. fumigatus and curdlan respectively, and the expression of dectin-1 and proinflammatory cytokines (IL-1β and TNF-α) were detected by RT-PCR, western blot and ELISA.
  
  
  RESULTS
  Dectin-1 mRNA and dectin-1 protein expression increased when HCECs were stimulated with A. fumigatus or curdlan, and CsA inhibited the dectin-1 expression both in mRNA and protein levels specifically. Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and CsA compared to pretreatment with CsA alone, while dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and CsA compared to pretreatment with CsA alone.
  
  
  CONCLUSIONS
  These data provide evidence that CsA can inhibit the expression of dectin-1 and proinflammatory cytokines through dectin-1 when HCECs are stimulated by A. fumigatus or curdlan. The active form of vitamin D, 1,25(OH)2D3, and VDR signaling pathway regulate the inhibition of CsA. The inhibition is enhanced by 1,25(OH)2D3, and the VDR inhibitor suppresses the inhibition.
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Guiqiu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.affiliation: Shandong Eye Institute, Qingdao, Shandong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cong
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000378:metabolism*; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D000942:Antigens, Bacterial; D002117:Calcitriol; D016572:Cyclosporine; D053583:Interleukin-1beta; D037181:Lectins, C-Type; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan