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: Hui Li, Jing Zhang, Ashok Kumar, Mei Zheng, Sally S Atherton, Fu-Shin X Yu
• Journal: Immunology (Immunology) Vol. 117 Issue 2 Pg. 167-76 (Feb 2006) ISSN: 0019-2805 [Print] England
• PMID: 16423052 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• NF-kappa B
• RNA, Messenger
• TLR7 protein, human
• Toll-Like Receptor 7
• Interferons

Topics

• Cells, Cultured
• Cytokines (biosynthesis, genetics)
• Epithelium, Corneal (immunology)
• Gene Expression
• Herpesvirus 1, Human
• Humans
• Interferons (biosynthesis, genetics)
• Keratitis, Herpetic (immunology)
• NF-kappa B (metabolism)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Toll-Like Receptor 7 (biosynthesis)