Intraparenchymal administration of interleukin-1beta induces cyclooxygenase-2-mediated expression of membrane- and cytosolic-associated prostaglandin E synthases in mouse brain

J Neuroimmunol. 2004 Mar;148(1-2):32-40. doi: 10.1016/j.jneuroim.2003.11.001.

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

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / drug effects*
  • Brain / enzymology
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytosol / drug effects
  • Cytosol / enzymology
  • Densitometry
  • Drug Interactions
  • Gene Expression / drug effects*
  • Gene Expression Regulation / drug effects*
  • Immunoblotting / methods
  • Immunoenzyme Techniques / methods
  • Interleukin-1 / pharmacology*
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nitrobenzenes / pharmacology
  • Prostaglandin-E Synthases
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sulfonamides / pharmacology
  • Time Factors

Substances

  • Chemokine CCL2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases