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HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9

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Abstract

Angiogenesis and inflammatory mediators are critical pathogenic factors in herpetic stromal keratitis (HSK). Since disease progresses without infectious virus, HSV-DNA and HSV-IgG complexes (HSV-IC) may contribute to HSK by triggering these factors. Production of VEGF and MMP-9 was studied in vitro using corneal epithelial cells (HCE), fibroblasts (HCRF) and macrophages (THP-1). VEGF was elevated in HCRF and THP-1 following treatment with HSV-DNA and HSV-IC. MMP-9 was elevated in THP-1 but not in corneal cells. When anti-HSV-IgG(Fab′)2 complexes stimulated THP-1, MMP-9 was reduced to control levels. Pretreatment of THP-1 with anti-TLR-2 and -3 inhibited MMP-9 production. Thus, HSV-IC may stimulate THP-1 through the Fc receptor and TLRs. Proinflammatory cytokines (IL-1b, IL-6, and TNF-α) increased VEGF and MMP-9 in corneal cells and macrophages. These studies indicate that the continued presence of HSV-DNA and HSV-IC contribute to angiogenesis and inflammation in HSK. Thus, cytokines and TLRs may be potential targets for intervention.

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Acknowledgments

We thank Dr. Chandraskharam Naginini for providing us HCRFs. This research was supported (in part) by the Intramural Research program of NIH National Eye Institute.

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Authors and Affiliations

  1. Immunology and Virology Section, Laboratory of Immunology, NEI, NIH, Bethesda, MD, 20892, USA

    Kozaburo Hayashi, Laura C. Hooper & John J. Hooks

  2. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

    Barbara Detrick

Authors
  1. Kozaburo Hayashi
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  2. Laura C. Hooper
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  3. Barbara Detrick
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  4. John J. Hooks
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Correspondence to Kozaburo Hayashi.

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Hayashi, K., Hooper, L.C., Detrick, B. et al. HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9. Arch Virol 154, 219–226 (2009). https://doi.org/10.1007/s00705-008-0303-7

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  • DOI: https://doi.org/10.1007/s00705-008-0303-7

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