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Angiogenesis in Viral Immunoinflammatory Lesions

Angiogenesis in Viral Immunoinflammatory Lesions

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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 2

  2. Which molecules are induced by HSV infection to mediate angiogenesis?

  3. INTRASTROMAL VEGF CAUSES NEOVASCULARIZATION 4 days post admin FITC labelled PECAM 1 monoclonal antibody

  4. VEGF expression after HSV-1 corneal infection VEGF in corneal lysate (pg/ml) Days p.i.

  5. a b c VEGF+ cells in HSV infected corneas Day 1 Day 8 Day 15

  6. Corneal Epithelial Cells VEGF+ GFP-HSV GFP-HSV M J774A.1 Cell Line VEGF production - a paracrine effect

  7. Effect of VEGF inhibition on HSV angiogenesis

  8. Since VEGF response to HSV is paracrine, how is it induced? • Some cellular or viral protein released from infected cell induces • Viral DNA with PAMP activity

  9. Bioactive DNA • Support: HSV DNA rich in potential bioactive CpGs • Doubts: • Would need to gain access to tissues from producer cells • Unexplored

  10. FITC-CpG stimulates VEGF production in J774A.1 cells Cytoplasm Nuclear Control ODN CpG ODN

  11. CpG ODN VEGF HSV DNA Vehicle Control DNA Control ODN HSV DNA and CpG ODN induce angiogenesis in mouse corneal micropocket assay

  12. HSV DNA induces angiogenesis in mouse corneal micropocket assay 2 1.5 Angiogenic Area (mm2) 1 0.5 0 VEGF 0.5 1 2 5g Sperm Vehicle HSV-DNA DNA

  13. Anti-VEGF suppresses HSV-DNA and CpG induced angiogenesis 1.5 1 Angiogenic Area (mm2) 0.5 0

  14. Conclusion • One mechanism by which the paracrine effect of HSV on VEGF production occurs could involve release of viral DNA

  15. To continue open the Part 3 • from Supercourse-Vet • htpp://centaur.vri.cz