Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Peptides
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Anti-Inflammatory Agents / pharmacology
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Azepines / pharmacology*
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Budesonide / pharmacology*
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Cell Line
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Cyclic N-Oxides
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Cyclooxygenase 2
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Drug Synergism
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Gene Expression Regulation, Enzymologic / drug effects
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Humans
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Interleukin-1
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Membrane Proteins
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Neurons / drug effects*
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Nitrogen Oxides / pharmacology*
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Peptide Fragments
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Platelet Aggregation Inhibitors / pharmacology
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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RNA / metabolism
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Stress, Physiological / chemically induced
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Stress, Physiological / metabolism*
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Thienopyridines
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Time Factors
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Transcriptional Activation
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Triazoles / pharmacology*
Substances
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Amyloid beta-Peptides
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Anti-Inflammatory Agents
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Azepines
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Cyclic N-Oxides
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Interleukin-1
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Membrane Proteins
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Nitrogen Oxides
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Peptide Fragments
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Platelet Aggregation Inhibitors
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Thienopyridines
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Triazoles
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amyloid beta-protein (1-42)
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BN 50730
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phenyl-N-tert-butylnitrone
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Budesonide
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RNA
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases