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

Objective: The objective of this study is to observe whether cyclosporine A(Cs A)inhibits the expression of Dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus(A.fumigatus)and to investigate the effect of VDR signaling pathway 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 Cs A for 12 h.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 m RNA and Dectin-1 protein expression increased when HCECs were stimulated with A.fumigatus or curdlan,and Cs A inhibited the Dectin-1 expression both in m RNA and protein levels specifically.Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and Cs A compared to pretreatment with Cs A alone,while Dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and Cs A compared to pretreatment with Cs A alone.Conclusion: 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 Cs A.The inhibition is enhanced by 1,25(OH)2D3,and the VDR inhibitor suppresses the inhibition.