ERK activation is required for double-stranded RNA- and virus-induced interleukin-1 expression by macrophages. J Biol Chem 2003 May 09;278(19):16683-9
Date
03/01/2003Pubmed ID
12609986DOI
10.1074/jbc.M211744200Scopus ID
2-s2.0-0038607935 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
Double-stranded (ds) RNA, which accumulates during viral replication, activates the antiviral response of infected cells. In this study, we have identified a requirement for extracellular signal-regulated kinase (ERK) in the regulation of interleukin 1 (IL-1) expression by macrophages in response to dsRNA and viral infection. Treatment of RAW 264.7 cells or mouse macrophages with dsRNA stimulates ERK phosphorylation that is first apparent following a 15-min incubation and persists for up to 60 min, the accumulation of iNOS and IL-1 mRNA following a 6-h incubation, and the expression of iNOS and IL-1 at the protein level following a 24-h incubation. Inhibitors of ERK activation prevent dsRNA-induced ERK phosphorylation and IL-1 expression by macrophages. The regulation of macrophage activation by ERK appears to be selective for IL-1, as ERK inhibition does not attenuate dsRNA-induced iNOS expression by macrophages. dsRNA stimulates both ERK activation and IL-1 expression by macrophages isolated from dsRNA-dependent protein kinase (PKR)-deficient mice, indicating that PKR does not participate in this antiviral response. These findings support a novel PKR-independent role for ERK in the regulation of the antiviral response of IL-1 expression and release by macrophages.
Author List
Maggi LB Jr, Moran JM, Buller RM, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiovirus Infections
Cells, Cultured
Encephalomyocarditis virus
Enzyme Inhibitors
Flavonoids
Interleukin-1
MAP Kinase Signaling System
Macrophage Activation
Macrophages, Peritoneal
Mice
Phosphorylation
RNA, Double-Stranded
eIF-2 Kinase
