title: Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells.
abstract: 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.
authors.affiliation: The Kresge Eye Institute/Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.forename: Sally S
authors.initials: SS
authors.lastname: Atherton
authors.forename: Fu-Shin X
authors.initials: FS
authors.lastname: Yu
mesh_terms: 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*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D007372:Interferons