Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria.
Cerebral malaria (CM) is a severe complication of malaria, in which cytokine production can produce immunopathological consequences. Cytokines can up-regulate prostaglandin synthesis via an increase in cyclooxygenase (COX) enzyme activity. We investigated the expression of COX enzymes, COX-1 and COX-2, in the brain by use of murine models of CM and of malaria without cerebral involvement. Although COX-1 mRNA was induced in the brain in both models of malaria, COX-2 mRNA was induced specifically in CM. Inhibition of COX-2 with celecoxib resulted in an earlier onset of CM. Treatment with celecoxib did not alter the outcome of malaria infection without cerebral involvement. These data suggest that induction of COX-2 expression and prostaglandin synthesis may have a protective effect in CM.
Ball
Helen J
HJ
Department of Pathology D06, University of Sydney, Camperdown, NSW 2006, Australia. helenb@med.usyd.edu.au
MacDougall
Hamish G
HG
McGregor
Iain S
IS
Hunt
Nicholas H
NH
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D016779:Malaria, Cerebral / Q000201:enzymology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone