title: Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms.
abstract: The processing and regulated secretion of IL-1beta are critical points of control of the biological activity of this important pro-inflammatory cytokine. IL-1beta is produced by both monocytes and macrophages, but the rate and mechanism of release differ according to the differentiation status and the origin of these cells. We aimed to study the control of processing and release in human blood monocytes and human monocyte-derived macrophages. Toll-like receptor (TLR)-induced IL-1beta production and release were investigated for dependence upon caspase-1, P2X7 receptor activation, and loss of membrane asymmetry associated with microvesicle shedding. TLR agonists induced P2X7 receptor-dependent IL-1beta release in both monocytes and macrophages; however, only monocytes also showed P2X7 receptor-independent release of mature IL-1beta. Furthermore, in monocytes ATP-mediated PS exposure could be activated independently of IL-1beta production. Release of IL-1beta from monocytes showed selectivity for specific TLR agonists and was accelerated by P2X7 receptor activation. Human monocytes released more IL-1beta/cell than macrophages. These data have important implications for inflammatory diseases that involve monocyte activation and IL-1 release.
authors.affiliation: Department of Cardiovascular Science, Royal Hallamshire Hospital, Beech Hill Rd., Sheffield S10 2RX, UK.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Ward
authors.forename: Peter W
authors.initials: PW
authors.lastname: West
authors.forename: Mark P
authors.initials: MP
authors.lastname: Ariaans
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Francis
authors.forename: David C
authors.initials: DC
authors.lastname: Crossman
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
authors.forename: Heather L
authors.initials: HL
authors.lastname: Wilson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013997:Time Factors; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists
chemical_list: D053583:Interleukin-1beta; C546468:P2RX7 protein, human; D010718:Phosphatidylserines; D011804:Quinolines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D000255:Adenosine Triphosphate; C037219:quinoline; D020170:Caspase 1