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Angiogenesis in Viral Immunoinflammatory Lesions

Angiogenesis in Viral Immunoinflammatory Lesions. Barry T. Rouse University of Tennessee Part 3. A second mechanism could involve signalling molecules made early after HSV infection IL-6 and IL-1 (Most cell genes turned off by infection).

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Angiogenesis in Viral Immunoinflammatory Lesions

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  1. Angiogenesis in Viral Immunoinflammatory Lesions Barry T. Rouse University of Tennessee Part 3

  2. A second mechanism could involve signalling molecules made early after HSV infection • IL-6 and IL-1 (Most cell genes turned off by infection)

  3. IL-6 administration into the corneal stroma causes angiogenesis • The effect is prevented by anti-VEGF

  4. IL-6 induces angiogenesis by up regulating VEGF production in the cornea IL-6 VEGF164 IL-6 + anti-mVEGF PBS

  5. IL-1 upregulates VEGF and VEGFR2 expression in corneas following HSV-1 infection VEGFR2 Real Time PCR VEGF ELISA IL-1Ra Tg IL-1Ra KO C57BL/6

  6. IL-1Ra Tg IL-1Ra Tg IL-1Ra K/O C57BL6 IL-1Ra K/O Angiogenesis score C57BL6 Days p.i. Blocking IL-1 activity reduces corneal angiogenesis following HSV-1 infection

  7. HSV Infection Autocrine production of signaling molecules (IL-6, IL-1) MIP-2 Signal Induction of VEGF PMN MMP-9 Corneal Neovascularization

  8. Possible role of MMP-9 in stromal keratitis (serves to degrade matrix so vessels can proceed into the stroma)

  9. HSV infection causes MMP-9 upregulation 2 days post infection WT virus (KOS) WT virus (RE) Mutant (ICP-4-/-) trauma UV virus naive MMP-9 MMP-2

  10. Infected corneas have MMP-9 expressing cells Histo Anti MMP-9

  11. Neutrophils are a likely source of MMP-9 Control IgG Anti Gr-1 MMP-9 MMP-2

  12. 5 20 129 Sv/Ev WT 4 MMP-9 K/O 15 3 Angiogenic scoring Severity 10 2 5 1 0 0 0 5 10 15 20 0 5 10 15 20 Days post infection MMP-9 KO mice show diminished angiogenesis and severity of HSK

  13. Effect of MMP-9 inhibitor, TIMP-1, on HSV induced angiogenesis 5 20 vector DNA 4 TIMP-1 DNA 15 3 Severity 10 Angiogenic scoring 2 5 1 0 0 0 5 10 15 20 0 5 10 15 20 Days post infection

  14. HSV induced angiogenesis involves multiple factors. These include VEGF, FGF (not shown), MIP-2 (not shown), and MMP-9

  15. To continue open the Part 4 • from Supercourse-Vet • htpp://centaur.vri.cz

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