Limmon Gino V, Arredouani Mohamed, McCann Kelly L, Corn Minor Radiah A, Kobzik Lester, Imani Farhad
NIEHS/NIH, Laboratory of Respiratory Biology, Durham, North Carolina 27709, USA.
FASEB J. 2008 Jan;22(1):159-67. doi: 10.1096/fj.07-8348com. Epub 2007 Aug 20.
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.
双链RNA（dsRNA）是宿主免疫系统识别正在进行的病毒感染的有力信号。细胞内或细胞外存在dsRNA会导致包括上皮细胞在内的多种细胞类型中诱导先天性炎性细胞因子。然而，识别细胞外dsRNA的细胞表面受体尚未确定。在此，我们报告细胞外dsRNA被A类清道夫受体（SR-A）识别并内化。用SR-A的特异性拮抗剂或抗SR-A抗体处理人上皮细胞可显著抑制dsRNA诱导的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-8以及活化正常T细胞表达和分泌调节因子（RANTES）。此外，对SR-A缺陷（SR-A(-/-)）小鼠进行鼻内dsRNA处理显示炎性细胞因子表达显著降低，肺中多形核白细胞（PMN）积累相应减少。这些数据提供了直接证据，表明SR-A是dsRNA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。
