Role of MAPK in the regulation of double-stranded RNA- and encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages. J Immunol 2006 Sep 01;177(5):3413-20
Date
08/22/2006Pubmed ID
16920983DOI
10.4049/jimmunol.177.5.3413Scopus ID
2-s2.0-33747756130 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
In response to virus infection or treatment with dsRNA, macrophages express the inducible form of cyclooxygenase-2 (COX-2) and produce proinflammatory prostaglandins. Recently, we have shown that NF-kappaB is required for encephalomyocarditis virus (EMCV)- and dsRNA-stimulated COX-2 expression in mouse macrophages. The dsRNA-dependent protein kinase R is not required for EMCV-stimulated COX-2 expression, suggesting the presence of protein kinase R-independent pathways in the regulation of this antiviral gene. In this study, the role of MAPK in the regulation of macrophage expression of cyclooxygenase-2 (COX)-2 in response to EMCV infection was examined. Treatment of mouse macrophages or RAW-264.7 cells with dsRNA or infection with EMCV stimulates the rapid activation of the MAPKs p38, JNK, and ERK. Inhibition of p38 and JNK activity results in attenuation while ERK inhibition does not modulate dsRNA- and EMCV-induced COX-2 expression and PGE2 production by macrophages. JNK and p38 appear to selectively regulate COX-2 expression, as inhibition of either kinase fails to prevent dsRNA- or EMCV-stimulated inducible NO synthase expression by macrophages. Using macrophages isolated from TLR3-deficient mice, we show that p38 and JNK activation and COX-2 expression in response to EMCV or poly(IC) does not require the presence the dsRNA receptor TLR3. These findings support a role for p38 and JNK in the selective regulation of COX-2 expression by macrophages in response to virus infection.
Author List
Steer SA, Moran JM, Christmann BS, Maggi LB Jr, 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
Cyclooxygenase 2
Dinoprostone
Encephalomyocarditis virus
Enzyme Activation
Gene Expression Regulation, Enzymologic
MAP Kinase Signaling System
Macrophages
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Nitric Oxide Synthase Type II
Phosphorylation
Poly I-C
RNA, Double-Stranded
Toll-Like Receptor 3
