HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9.
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-alpha) 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.
Hayashi
Kozaburo
K
Immunology and Virology Section, Laboratory of Immunology, NEI, NIH, Bethesda, MD 20892, USA. hayashik@nei.nih.gov
Hooper
Laura C
LC
Detrick
Barbara
B
Hooks
John J
JJ
D000914:Antibodies, Viral / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology / Q000821:virology; D016510:Corneal Neovascularization / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000494:pharmacology; D004279:DNA, Viral / Q000276:immunology / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016849:Keratitis, Herpetic / Q000150:complications / Q000276:immunology* / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009500:Neutralization Tests; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D016207:Cytokines; D004279:DNA, Viral; D007074:Immunoglobulin G; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9