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S. Takeda, D. Miyazaki, Y. Terasaka, K. Yakura, S. Yamagami, Y. Inoue; Roles of Toll-Like Receptor-9 in Transcriptional Networks in Corneal Endothelial Cells After Herpes Simplex Virus Type 1 Infection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3866.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the transcriptional responses of human corneal endothelial cells (HCEs) after herpes simplex virus type 1 (HSV-1) infection and to examine the roles of critical inflammatory element(s).
Immortalized HCEs were infected with HSV-1, and the global transcriptional profile determined. Molecular signaling networks were constructed from the HSV-1-induced transcriptomes. The relationships of the crucial molecules in the identified networks were examined by FACS, real time-PCR, and ELISA.
HSV-1 infection induced a global transcriptional activation with 873 genes significantly induced or repressed compared to mock infected HCEs (P<0.05, 3< or 0.33> threshold). Network analysis identified viral infection-induced interferon response and pattern recognition receptor(PRR)-mediated signaling as most significant association in the global transcriptional responses. To understand initial events underlying HSV-1 infection, we screened for expression of toll-like receptors(TLR) as representative PRR. FACS analysis identified selective expression of TLR-9 in HCE. In the inflammatory networks, type I interferon and IL-6 was identified as crucial elements. Analysis using TLR-9-inhibitory oligonucleotide or siRNA showed that TLR-9 inhibition reduced HSV replication, and suppressed transcritptional activation of IL-6 in HCEs.
HCEs respond to HSV-1 infection by TLR9, which induces IL-6 as crucial element in the inflammatome.
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