Abstract
Interleukin (IL)-1beta is a proinflammatory cytokine expressed in neural tissue following injury and in neurodegenerative states. To understand the consequences of its presence in brain, we carried out intraparenchymal IL-1beta injections and found significant increases in prostaglandin (PG)E2, a critical factor in inflammatory and physiological processes. Elevated mRNA and protein expression of the PGE2-synthetic-related enzymes cyclooxygenase (COX)-2 and membrane-associated PGE synthase (PGES) accompanied local PGE2 production. In addition, IL-1beta stimulated protein expression of cytosolic PGES. Finally, we showed attenuation of these IL-1beta-inductions by COX-2 inhibition, suggesting in vivo regulation of both PGE synthase isoforms in the brain.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / cytology
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Brain / drug effects*
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Brain / enzymology
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Cell Membrane / drug effects
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Cell Membrane / enzymology
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Cytosol / drug effects
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Cytosol / enzymology
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Densitometry
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Drug Interactions
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Gene Expression / drug effects*
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Gene Expression Regulation / drug effects*
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Immunoblotting / methods
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Immunoenzyme Techniques / methods
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Interleukin-1 / pharmacology*
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / metabolism*
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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Male
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Membrane Proteins
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Mice
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Mice, Inbred C57BL
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Nitrobenzenes / pharmacology
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Prostaglandin-E Synthases
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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RNA, Messenger / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Sulfonamides / pharmacology
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Time Factors
Substances
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Chemokine CCL2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Interleukin-1
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Isoenzymes
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Membrane Proteins
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Nitrobenzenes
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RNA, Messenger
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Cyclooxygenase 1
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, mouse
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Intramolecular Oxidoreductases
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Prostaglandin-E Synthases