title: Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin-10, but not interleukin-1 alpha or tumour necrosis factor-alpha.
abstract: Herpes simplex virus (HSV) is known to possess several mechanisms whereby it can evade the normal host immune defences. In this study the expression of the immunosuppressive cytokine, interleukin (IL)-10, was monitored following infection of a murine keratinocyte cell line (PAM-212) and compared with the expression of two proinflammatory cytokines: IL-1 alpha and tumour necrosis factor (TNF)-alpha. The PAM-212 cells were infected at a multiplicity of 0.5 with a clinical isolate of HSV type 1, and the mRNA of the three cytokines was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) over the following 24 hr. By 12 hr postinfection the amount of IL-10 mRNA had increased significantly to five-fold greater than that found in uninfected cells (P < 0.01), and this elevated level was maintained until at least 24 hr postinfection. In contrast, IL-1 alpha and TNF-alpha mRNAs were not significantly up-regulated by the HSV infection. Immunostaining with an IL-10 monoclonal antibody (mAb) revealed that cytoplasmic IL-10 protein had increased by 6-12 hr postinfection. This quantity was further increased at 24 hr postinfection, when the viral cytopathic effect was apparent. Viral replication was necessary, but not sufficient on its own, for IL-10 induction. Experiments with HSV mutants lacking functional transactivating factors suggested that the viral transactivating proteins ICP-0 and VP-16 may be necessary for HSV-induced IL-10 expression. Thus, the up-regulation in the expression of IL-10 mRNA and protein induced by HSV early in the infection of keratinocytes represents a specific response and may be part of the viral strategy to avoid local immune defence mechanisms in the skin.
authors.affiliation: Department of Dermatology, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Zak-Prelich
authors.forename: K E
authors.initials: KE
authors.lastname: Halliday
authors.forename: C
authors.initials: C
authors.lastname: Walker
authors.forename: C M
authors.initials: CM
authors.lastname: Yates
authors.forename: M
authors.initials: M
authors.lastname: Norval
authors.forename: R C
authors.initials: RC
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000276:immunology*; D007108:Immune Tolerance; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000276:immunology / Q000821:virology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10