Src family kinases participate in the regulation of encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages.
Src family kinases (SFKs) are non-receptor tyrosine kinases that have been implicated as regulators of the inflammatory response. In this study, the role of SFK activation in the inflammatory response of macrophages to encephalomyocarditis virus (EMCV) infection was examined. Virus infection of macrophages stimulates the expression of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta and inducible nitric oxide synthase (iNOS). Inhibition of SFK attenuates EMCV-induced COX-2 expression and prostaglandin E(2) production, iNOS expression and subsequent nitric oxide production, and IL-1beta expression. EMCV-induced COX-2 expression requires the activation of nuclear factor-kappaB and the mitogen-activated protein kinase p38. Consistent with these previous findings, inhibition of SFKs attenuated the phosphorylation of p38 in response to EMCV infection, suggesting that SFKs may act upstream of p38. These findings provide evidence that SFK activation plays an active role in the regulation of inflammatory gene expression by virus-infected macrophages.
Freudenburg
Wieke
W
Edward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, MO, USA.
Buller
R Mark L
RM
Corbett
John A
JA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D004789:Enzyme Activation; D054884:Host-Pathogen Interactions; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D017931:DNA Primers; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone