title: Scavenger receptor class-A is a novel cell surface receptor for double-stranded RNA.
abstract: 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.
authors: NIEHS/NIH, Laboratory of Respiratory Biology, Durham, North Carolina 27709, USA.
authors: Gino V
authors: GV
authors: Limmon
authors: Mohamed
authors: M
authors: Arredouani
authors: Kelly L
authors: KL
authors: McCann
authors: Radiah A
authors: RA
authors: Corn Minor
authors: Lester
authors: L
authors: Kobzik
authors: Farhad
authors: F
authors: Imani
mesh_terms: D000818:Animals; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017931:DNA Primers; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D012330:RNA, Double-Stranded / Q000378:metabolism*; D011869:Radioligand Assay; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D012330:RNA, Double-Stranded; D051116:Receptors, Scavenger