Induction of interleukin-1 production by ligands binding to the scavenger receptor in human monocytes and the THP-1 cell line.
Foam cell formation via lipid accumulation through the scavenger receptor in human monocyte/macrophages is believed to be one of the earliest events in atherogenesis. In this study we demonstrate that stimulation of the scavenger receptor activates monocytes to produce interleukin-1 (IL-1). Polyinosinic acid (poly I) and fucoidan, both ligands known to bind to the scavenger receptor, induced IL-1 beta production in human monocytes. Polycytidylic acid, a structurally related compound to poly I, which does not bind to the scavenger receptor, was used as a negative control and had virtually no effect on IL-1 production. THP-1 cells, which normally do not express scavenger receptors, were almost unresponsive to poly I and fucoidan. PMA priming, which has been reported to up-regulate scavenger receptor expression in THP-1 cells, significantly enhanced IL-1 production by fucoidan and poly I. IL-1 produced by scavenger receptor stimulation was shown to be secreted extracellularly, and biologically active. Scavenger receptor-mediated IL-1 production was inhibited by H7, a protein kinase C inhibitor, and enhanced by IBMX, an inhibitor of cyclic AMP degradation, suggesting a synergistic effect of protein kinase C and cyclic AMP-mediated signal transduction pathways in scavenger receptor-mediated IL-1 production. Due to the potentially deleterious effects of IL-1 on the vessel wall, IL-1 produced by ligand binding to the scavenger receptor in human monocytes may play a role in the pathogenesis of atherosclerosis.
Palkama
T
T
Department of Bacteriology and Immunology, University of Helsinki, Finland.
D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008024:Ligands; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate