Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells.
Herpetic epithelial and stromal keratitis is a sight-threatening ocular infection. To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV-1) infection of the cornea, we used a telomerase-immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV-1 (KOS strain). HSV-1 infection of HCECs resulted in a two-phase activation of nuclear factor-kappaB (NF-kappaB), JNK and p38, with the first peak at 1-4 hr and a second peak at 8 hr. Concomitant with the first peak of activation, transcriptional expression of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-alpha and interferon (IFN)-beta was rapidly induced in HSV-1-infected cells. HSV-1 infection also induced the production of IL-6, IL-8, and TNF-alpha in both HUCL cells and primary HCECs. Coincident with the second phase of NF-kappaB activation in HSV-1-infected HCECs, the expression of Toll-like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly down-regulated. Thus, in response to HSV-1 infection, HCECs produce proinflammatory cytokines, leading to infiltration, and IFNs to enhance the antiviral activity in the cornea, probably through sequential activation of TLRs.
Li
Hui
H
The Kresge Eye Institute/Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Zhang
Jing
J
Kumar
Ashok
A
Zheng
Mei
M
Atherton
Sally S
SS
Yu
Fu-Shin X
FS
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D019573:Epithelium, Corneal / Q000276:immunology*; D015870:Gene Expression; D018259:Herpesvirus 1, Human; D006801:Humans; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D016849:Keratitis, Herpetic / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis*
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D007372:Interferons