Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci.
Group B streptococcal (GBS) infections are associated with high morbidity and mortality. The molecular pathways mediating the pathophysiological events in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the effects of GBS on eicosanoid metabolism and regulatory mechanisms, we exposed human monocytes to GBS and found that they secreted prostaglandin E2, prostacyclin, and thromboxane A2. Exposure to GBS caused monocytes to express COX-2 mRNA and protein in both a time- and concentration-dependent manner that correlated with eicosanoid production. COX-1 protein was unchanged. Addition of the anti-inflammatory cytokines interleukin (IL)-4 or IL-10 markedly attenuated GBS-induced COX-2 protein accumulation after GBS exposure, as did inhibition of p38 MAPK. Our experiments are the first to show that exposure of monocytes to a gram-positive bacterium (GBS) results in induction of functional COX-2, suggesting that eicosanoids may play important roles in the pathogenesis of GBS infections.
Maloney
C G
CG
Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City 84132, USA. chris.maloney@hci.utah.edu
Thompson
S D
SD
Hill
H R
HR
Bohnsack
J F
JF
McIntyre
T M
TM
Zimmerman
G A
GA
D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D004926:Escherichia coli; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007527:Isoenzymes / Q000097:blood* / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood* / Q000235:genetics; D011453:Prostaglandins / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000472:pathogenicity / Q000502:physiology*; D013931:Thromboxanes / Q000097:blood; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
D005419:Flavonoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011453:Prostaglandins; D011994:Recombinant Proteins; D013931:Thromboxanes; D016753:Interleukin-10; D015847:Interleukin-4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one