Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA
Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA
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DOI：
10.1096/fj.07-8348com
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发表时间：
2008-01-01
期刊：
影响因子：
4.8
通讯作者：
Imani, Farhad
中科院分区：
文献类型：
--
作者：
Limmon, Gino V.;Arredouani, Mohamed;Imani, Farhad
双链RNA（dsRNA）是针对正在进行的病毒感染的存在的宿主免疫系统的有效信号。细胞内或细胞外dsRNA的存在导致在包括上皮细胞在内的许多细胞类型中诱导先天性炎性细胞因子。然而，用于识别胞外dsRNA的细胞表面受体尚未确定。在这里，我们报告，细胞外dsRNA的识别和内化清道夫受体A类（SR-A）。用SR-A的特异性拮抗剂或用抗SR-A抗体处理人上皮细胞显著抑制肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-8的dsRNA诱导，并调节正常T细胞表达和分泌的活化（RANTES）。此外，SR-A缺陷（SR-A（-/-））小鼠的鼻内dsRNA治疗显示炎性细胞因子表达显著降低，肺中多形核白细胞（PMN）的积累相应减少。这些数据提供了直接证据，表明SR-A是双链RNA的新型细胞表面受体，因此，SR-A可能在抗病毒免疫反应中发挥作用。利蒙湾五、Arredouani，M.，麦肯K. L.，小科恩河一、科布兹克湖伊马尼湖A类清道夫受体是一种新型的双链RNA细胞表面受体。
Double-stranded RNA (dsRNA) is a potent signal to the host immune system for the presence of an ongoing viral infection. The presence of dsRNA, intracellularly or extracellularly, leads to the induction of innate inflammatory cytokines in many cell types including epithelial cells. However, the cell surface receptor for recognition of extracellular dsRNA is not yet determined. Here, we report that extracellular dsRNA is recognized and internalized by scavenger receptor class-A (SR-A). Treatment of human epithelial cells with specific antagonists of SR-A or with an anti-SR-A antibody significantly inhibited dsRNA induction of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and regulated on activation normal T-cell expressed and secreted (RANTES). Furthermore, intranasal dsRNA treatment of SR-A-deficient (SR-A(-/-)) mice showed a significant decrease in the expression of inflammatory cytokines and a corresponding decrease in the accumulation of polymorphonuclear leukocytes (PMNs) in lungs. These data provide direct evidence that SR-A is a novel cell surface receptor for dsRNA, and therefore, SR-A may play a role in antiviral immune responses.-Limmon, G. V., Arredouani, M., McCann, K. L., Corn Minor, R. A., Kobzik, L., Imani, L. Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA.