title: Augmented expression of platelet-activating factor receptor gene by TNF-alpha through transcriptional activation in human monocytes.
abstract: Tumor necrosis factor alpha (TNF-alpha) is a cytokine produced by activated monocytes and often associated with platelet-activating factor (PAF) during the pathogenesis of many inflammatory and infectious diseases. 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 stimulation and persisted up to 24 h. Actinomycin D pretreatment studies revealed a transcriptional increase in PAFR gene expression without effect on mRNA half-life. [3H]WEB 2086 binding studies showed a significant (43%) increase in specific binding sites in 24-h-treated cells without change in receptor affinity. Increased interleukin-6 production in response to PAF was also found in 24-h TNF-alpha-pretreated monocytes. These observations provide new evidence for TNF-alpha and PAF interactions in human monocytes during inflammatory processes through up-regulation of PAFR expression by TNF-alpha.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Dagenais
authors.forename: M
authors.initials: M
authors.lastname: Thivierge
authors.forename: J L
authors.initials: JL
authors.lastname: Parent
authors.forename: J
authors.initials: J
authors.lastname: Stankova
authors.forename: M
authors.initials: M
authors.lastname: Rola-Pleszczynski
mesh_terms: D001381:Azepines / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015533:Transcriptional Activation; D014230:Triazoles / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D001381:Azepines; D015850:Interleukin-6; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C052518:WEB 2086