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.