1 / 15

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).

dorit
Download Presentation

Angiogenesis in Viral Immunoinflammatory Lesions

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related