Effects Of AtRA And RARβ On Antifungal Innate Immunity Of Dectin-1-mediated Corneal Epithelial Cells

Purpose:To expose the effects of all trans-retinoic acid (atRA) and retinoic acid receptor β (RARβ) on Dectin-1 mediated innate antifungal immune responses in human corneal epithelial cells exposed to Aspergillus fumigates (A. fumigatus).Methods:RARβ mRNA and protein levels in normal and A. fumigatus stimulated human corneal epithelial cells (HCECs) were tested by RT-qPCR and Western blot. HCECs pretreated with or without atRA (10-6M,10-7M or 10-8M) were stimulated by A. fumigatus, the expression of Dectin-1, TNF-α and IL-6 were tested by RT-qPCR, Western blot and ELISA. HCECs were pretreated with RARP inhibitor LEI35 and agonist CD2314 before atRA and A. fumigatus infected and the expression of Dectin-1 were tested by PCR and western-blot respectively.Results:RARβ expressed in the normal and A. fumigatus infected HCECs and the differences in expression between these two groups were significant (P<0.001). RARβ mRNA expression was peaked at 8 hours. The level of RARP protein reached peak at 16 hours. Pretreatment of atRA significantly downregulated A. fumigatus induced Dectin-1, IL-6 and TNF-α expression after stimulated at 12h. LE135 inhibits the downregulation of Dectin-1 induced by atRA. Pretreated of CD2314 downregulated Dectin-1 expression after A. fumigatus stimulation.Conclusions:RARβ exists in human corneal epithelium and the expression increased after A. fumigatus stimulation. atRA can inhibit the expression of Dectin-1 and pro-inflammatory cytokines, which depends on RARP mediated the role of Dectin-1 mediated innate antifungal immune responses.