Synergism in the repression of COX-2- and TNFalpha-induction in platelet activating factor-stressed human neural cells.

Platelet activating factor (PAF; beta-acetyl-gamma-O-hexadecyl-l-alpha-phosphatidylcholine) triggers a rapid pro-inflammatory gene expression program in primary cultures of human neural (HN) cells. Two genes and gene products consistently induced after PAF treatment are the cytosoluble prostaglandin synthase cycloooxygenase-2 (COX-2) and the pro-apoptotic tumor necrosis factor alpha (TNFalpha). Both of these mediators are associated with the activation of inflammatory signaling, neural cell dysfunction, apoptosis and brain cell death, and both have been found to be up-regulated after brain injury in vivo.

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.