AUGMENTED EXPRESSION OF PLATELET-ACTIVATING-FACTOR RECEPTOR GENE BY TNF-ALPHA THROUGH TRANSCRIPTIONAL ACTIVATION IN HUMAN MONOCYTES

Tumor necrosis factor alpha (TNF-alpha) is a cytokine produced by acti vated monocytes and often associated with platelet-activating factor ( PAF) during the pathogenesis of many inflammatory and infectious disea ses, PAFR is a G-protein-coupled receptor constitutively expressed on monocytes, TNF-alpha (100-400 U/mL) significantly increased PAFR mRNA expression in human monocytes, This increase was seen after 1 h of sti mulation and persisted up to 24 h, Actinomycin D pretreatment studies revealed a transcriptional increase in PAFR gene expression without ef fect on mRNA half-life. [H-3]WEB 2086 binding studies showed a signifi cant (43%) increase in specific binding sites in 24-h-treated cells wi thout change in receptor affinity, Increased interleukin-6 production in response to PAF was also found in 24-h TNF-alpha-pretreated monocyt es. These observations provide new evidence for TNF-alpha and PAF inte ractions in human monocytes during inflammatory processes through upre gulation of PAFR expression by TNF-alpha.