May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
HSV-IgG(Immune-Complex:IC) and HSV DNA Elicit Angiogenic VEGF in Corneal Fibroblasts and Monocytes, While MMP-9 Is Produced Only in Monocytes
Author Affiliations & Notes
  • K. Hayashi
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • L. C. Hooper
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • B. Detrick
    Johns Hopkins University, Baaltimore, Maryland
  • J. J. Hooks
    Immunology/Virology, National Eye Inst/NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships K. Hayashi, None; L.C. Hooper, None; B. Detrick, None; J.J. Hooks, None.
  • Footnotes
    Support Supported by NEI intramural programme
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 731. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      K. Hayashi, L. C. Hooper, B. Detrick, J. J. Hooks; HSV-IgG(Immune-Complex:IC) and HSV DNA Elicit Angiogenic VEGF in Corneal Fibroblasts and Monocytes, While MMP-9 Is Produced Only in Monocytes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):731.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose:: In the herpetic stromal keratitis (HSK), viral DNA and IC are present in the cornea and induce the proinflammatory cytokine IL-6 in corneal cells via Toll-like receptor 9 (J. Gen. Virol., 2006 87: 2161). Vascular endothelial growth factor (VEGF) and the tissue damaging enzyme matrix metalloproteinase 9 (MMP-9) are known angiogenic factors involved in the pathogenesis of HSK.Here we ask if HSV DNA and HSV neutralized IC induce the production of VEGF and MMP-9 by corneal cells and human macrophage-monocytic cells (THP-1).

Methods:: THP-1 cells, corneal epithelial cells (HCE) and primary corneal fibroblasts (HCRF) were transfected with HSV-1 (McKrae and MP strain) DNA or treated with HSV-IgG(IC). After 24 hours incubation, supernatants were harvested and tested for the presence of VEGF and MMP-9 by ELISA.

Results:: HCRF produced large amount of VEGF (1,000pg/ml) after transfection with HSV-DNA or with the treatment of IC (McKrae IC: 1,650pg/ml and MP IC: 1,500pg/ml), however no VEGF was found in the supernatant of HCRF after active viral or UV inactivated viral infection. In contrast, HCE did not produce VEGF with HSV-DNA or IC, although a small amount of VEGF was detected in the supernatant of HCE with infection of both the McKrae and MP strain of HSV or UV-HSV. THP-1 cells produced a moderate amount of VEGF when infected with live or UV inactivated HSV. The MP strain is a more potent producer in THP-1 cells. In the supernatant of THP-1 cells transfected with MP DNA or treated with McKrae or MP IC, large amount of VEGF was found (MP DNA: 740pg/ml, McKrae or MP IC: 1,000-1,180pg/ml). HCE and HCRF did not produce MMP-9 after infection with live or UV- HSV,transfection with viral DNA or treatment with IC. However, MMP-9 is constitutively produced in the supernatant obtained from THP-1 cells (25ng/ml). When THP-1 cells were transfected with MP-DNA or treated with MP-IC, 2-2.5 times more MMP-9 was found in the supernatant.

Conclusions:: VEGF and MMP-9 were produced in response to HSV DNA transfection and IC treatment. Corneal fibroblasts and infiltrating monocyte -macrophages are shown to be the major producers of these angiogenic factors upon exposure to these viral components.

Keywords: herpes simplex virus • keratitis • microbial pathogenesis: experimental studies 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×