Budesonide epimer R, LAU-8080 and phenyl butyl nitrone synergistically repress cyclooxygenase-2 induction in [IL-1beta+Abeta42]-stressed human neural cells.
Interleukin-1beta (IL-1beta) and amyloid-beta peptide 42 (Abeta42) together induce a robust proinflammatory gene expression program in human neural cells in primary culture. One consistent genetic marker for this triggered inflammatory response is an increase in the expression of cycloooxygenase-2 (COX-2), a prostaglandin synthase also found to be up-regulated in neurological disorders such as Alzheimer's disease. In this study we provide data illustrating the combined effect of three independent classes of compounds: the glucocorticoid budesonide epimer R, the platelet-activating factor antagonist LAU-8080, and the free radical scavenger phenyl butyl nitrone, upon COX-2 gene activation and prostaglandin E2 (PGE2) levels in [IL-1beta+Abeta42]-stressed HN cells. The data indicate that specific combinations of repressors of COX-2 activity are synergistic in modulating the stress-induced up-regulation of COX-2 and PGE2, and this may be of potential therapeutic value in the design of treatment for complex neuroinflammatory disorders.
Boedker
Merete
M
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK 2100 Copenhagen, Denmark.
Boetkjaer
Anja
A
Bazan
Nicolas G
NG
Cui
Jian-Guo
JG
Zhao
Yuhai
Y
Pelaez
Ricardo Palacios
RP
Lukiw
Walter J
WJ
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002460:Cell Line; D003497:Cyclic N-Oxides; D051546:Cyclooxygenase 2; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1; D008565:Membrane Proteins; D009474:Neurons / Q000187:drug effects*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism*; D058924:Thienopyridines; D013997:Time Factors; D015533:Transcriptional Activation; D014230:Triazoles / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D001381:Azepines; D003497:Cyclic N-Oxides; D007375:Interleukin-1; D008565:Membrane Proteins; D009589:Nitrogen Oxides; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D058924:Thienopyridines; D014230:Triazoles; C075222:amyloid beta-protein (1-42); C066686:BN 50730; C029217:phenyl-N-tert-butylnitrone; D019819:Budesonide; D012313:RNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases