IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA
IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA
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DOI：
10.4049/jimmunol.0802683
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发表时间：
2009-02-15
影响因子：
4.4
通讯作者：
Hsu, Kenneth
中科院分区：
文献类型：
--
作者：
Endoh, Yasumi;Chung, Yuen Ming;Hsu, Kenneth
S100钙结合蛋白S100A8和S100A9在病毒感染患者中呈全身性升高。S100A8-S100A9复合体促进了潜伏感染HIV-1和S100A8诱导的HIV-1转录活性的人CD4(+)T淋巴细胞中的病毒复制。诱导S100基因的机制和病毒激活后这些蛋白的潜在来源尚不清楚。在这项研究中，我们发现在小鼠巨噬细胞中S100A8，在人单核细胞和巨噬细胞中，S100A8和S100A9被dsRNA模拟物多肌苷：多胞苷诱导。诱导是在转录水平上进行的，并且依赖于IL-10。与内毒素诱导的S100A8相似，dsRNA的诱导依赖于p38和ERK MAPK。蛋白激酶R(PKR)介导抗病毒防御，并参与TLR4或TLR3触发的MyD88依赖/独立信号转导。与IL-10一样，多聚肌苷：多胞苷和脂多糖诱导的S100也可被PKR特异性抑制剂2-氨基嘌呤抑制，提示有一条新的IL-10、PKR依赖途径。其他介质，如与dsRNA协同的干扰素-β，也可能参与其中。C/EBPβ结合所定义的启动子区域以响应dsRNA。S100A8在感染流感病毒的小鼠肺组织中表达，第8天达到高峰，在呼吸道上皮细胞和单个核细胞中有较强的免疫反应，并在恢复早期下降，表明在感染消退过程中受到上调的介体(S)的下调。IL-10与病毒持久性有关。由于S100A8/S100A9水平可能在IL-10升高的情况下保持不变，这些蛋白可能有助于某些RNA病毒感染患者的病毒持久性。免疫学杂志，2009,182：2258-2268。
The S100 calcium-binding proteins S100A8 and S100A9 are elevated systemically in patients with viral infections. The S100A8-S100A9 complex facilitated viral replication in human CD4(+) T lymphocytes latently infected with HIV-1- and S100A8-induced HIV-1 transcriptional activity. Mechanisms inducing the S100 genes and the potential source of these proteins following viral activation are unknown. In this study, we show that S100A8 was induced in murine macrophages, and S100A8 and S100A9 in human monocytes and macrophages, by polyinosinic: polycytidylic acid, a dsRNA mimetic. Induction was at the transcriptional level and was IL-10 dependent. Similar to LPS-induced S100A8, induction by dsRNA was dependent on p38 and ERK MAPK. Protein kinase R (PKR) mediates antiviral defense and participates in MyD88-dependent/independent signaling triggered by TLR4 or TLR3. Like IL-10, S100 induction by polyinosinic:polycytidylic acid and by LPS was inhibited by the specific PKR inhibitor 2-aminopurine, indicating a novel IL-10, PKR-dependent pathway. Other mediators such as IFN-beta, which synergized with dsRNA, may also be involved. C/EBP beta bound the defined promoter region in response to dsRNA. S100A8 was expressed in lungs of mice infected with influenza virus and was maximal at day 8 with strong immunoreactivity in epithelial cells lining the airways and in mononuclear cells and declined early in the recovery phase, implying down-regulation by mediator(s) up-regulated during resolution of the infection. IL-10 is implicated in viral persistence. Since S100A8/S100A9 levels are likely to be maintained in conditions where IL-10 is raised, these proteins may contribute to viral persistence in patients infected by some RNA viruses. The Journal of Immunology, 2009, 182: 2258-2268.