Activation of toll like receptor-3 induces corneal epithelial barrier dysfunction.
The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1.
Department of Ophthalmology, General Hospital of Jinan Military Command, Jinan 250031, China.
Jie
J
Wei
Department of Ophthalmology, General Hospital of Jinan Military Command, Jinan 250031, China. Electronic address: huarjiang@outlook.com.
Hua
H
Jiang
Department of Ophthalmology, General Hospital of Jinan Military Command, Jinan 250031, China.
Hongrui
H
Gao
Department of Ophthalmology, General Hospital of Jinan Military Command, Jinan 250031, China.
Guangjie
G
Wang
D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D019573:Epithelium, Corneal / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D010539:Permeability; D010766:Phosphorylation; D011070:Poly I-C / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
D017931:DNA Primers; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D056284:Histone Deacetylase 1; D011070:Poly I-C
Cornea; E-cadherin; Epithelial barrier; Histone deacetylase; Toll like receptor 3