Faculty Collaboration Database

Regulation of cyclooxygenase-2 expression by macrophages in response to double-stranded RNA and viral infection. J Immunol 2003 Jan 15;170(2):1070-6

Date

01/09/2003

Pubmed ID

12517975

DOI

10.4049/jimmunol.170.2.1070

Scopus ID

2-s2.0-0037438348 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

In this study the regulation of macrophage expression of cyclooxygenase-2 (COX-2) in response to dsRNA and virus infection was examined. Treatment of RAW 264.7 macrophages with dsRNA results in COX-2 mRNA accumulation and protein expression and the production of PGE(2). Similar to dsRNA, encephalomyocarditis virus (EMCV) infection of RAW 264.7 cells stimulates COX-2 expression and PGE(2) accumulation. The dsRNA-dependent protein kinase (PKR), which has been shown to participate in the regulation of gene expression in response to dsRNA and virus infection, does not appear to participate in the regulation of COX-2 expression by macrophages. Expression of dominant negative mutants of PKR in RAW 264.7 cells fails to attenuate dsRNA- and EMCV-induced COX-2 expression or PGE(2) production. Furthermore, dsRNA and EMCV stimulate COX-2 expression and PGE(2) accumulation to similar levels in macrophages isolated from wild-type and PKR-deficient mice. Recently, a novel PKR-independent role for the calcium-independent phospholipase A(2) (iPLA(2)) in the regulation of inducible NO synthase expression by macrophages in response to virus infection has been identified. The selective iPLA(2) suicide substrate inhibitor bromoenol lactone prevents dsRNA- and EMCV-stimulated inducible NO synthase expression; however, bromoenol lactone does not attenuate dsRNA- or EMCV-induced COX-2 expression by macrophages. In contrast, inhibition of NF-kappaB activation prevents dsRNA-stimulated COX-2 expression and PGE(2) accumulation by macrophages. These findings indicate that virus infection and treatment with dsRNA stimulate COX-2 expression by a mechanism that requires the activation of NF-kappaB and that is independent of PKR or iPLA(2) activation.

Author List

Steer SA, Moran JM, Maggi LB Jr, Buller RM, Perlman H, Corbett JA

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoviridae
Animals
Calcium
Cell Line
Cyclooxygenase 2
Encephalomyocarditis virus
Enzyme Induction
Interferon-gamma
Isoenzymes
Macrophages
Macrophages, Peritoneal
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B
Phospholipases A
Prostaglandin-Endoperoxide Synthases
RNA, Double-Stranded
eIF-2 Kinase