HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9
HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9
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DOI：
10.1007/s00705-008-0303-7
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发表时间：
2009-02-01
影响因子：
2.7
通讯作者：
Hooks, John J.
中科院分区：
文献类型：
--
作者：
Hayashi, Kozaburo;Hooper, Laura C.;Hooks, John J.
血管生成和炎症介质是疱疹性基质性角膜炎（HSK）的关键致病因素。由于疾病在没有传染性病毒的情况下进展，HSV-DNA 和 HSV-IgG 复合物 (HSV-IC) 可能通过触发这些因素而促成 HSK。使用角膜上皮细胞 (HCE)、成纤维细胞 (HCRF) 和巨噬细胞 (THP-1) 体外研究 VEGF 和 MMP-9 的产生。 HSV-DNA 和 HSV-IC 治疗后 HCRF 和 THP-1 中 VEGF 升高。 MMP-9 在 THP-1 中升高，但在角膜细胞中没有升高。当抗 HSV-IgG(Fab')(2) 复合物刺激 THP-1 时，MMP-9 降低至对照水平。用抗TLR-2和-3预处理THP-1可抑制MMP-9的产生。因此，HSV-IC 可能通过 Fc 受体和 TLR 刺激 THP-1。促炎细胞因子（IL-1b、IL-6 和 TNF-α）增加角膜细胞和巨噬细胞中的 VEGF 和 MMP-9。这些研究表明，HSV-DNA 和 HSV-IC 的持续存在有助于 HSK 中的血管生成和炎症。因此，细胞因子和 TLR 可能是潜在的干预目标。
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.