Temporal Interleukin-1β Secretion from Primary Human Peripheral Blood Monocytes by P2X7-independent and P2X7-dependent Mechanisms

被引:51
作者
Ward, Jon R. [1 ]
West, Peter W. [2 ]
Ariaans, Mark P. [1 ]
Parker, Lisa C. [2 ]
Francis, Sheila E. [1 ]
Crossman, David C. [1 ]
Sabroe, Ian [2 ]
Wilson, Heather L. [1 ]
机构
[1] Univ Sheffield, Royal Hallamshire Hosp, Sch Med, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England
[2] Univ Sheffield, Royal Hallamshire Hosp, Sch Med, Dept Infect & Immun, Sheffield S10 2RX, S Yorkshire, England
基金
英国医学研究理事会;
关键词
P2X(7) RECEPTOR; IL-1-BETA RELEASE; MICROGLIAL CELLS; P2X7; RECEPTORS; MESSENGER-RNA; DYE UPTAKE; ATP; INFLAMMASOME; EXPRESSION; ACTIVATION;
D O I
10.1074/jbc.M109.072793
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The processing and regulated secretion of IL-1 beta are critical points of control of the biological activity of this important pro-inflammatory cytokine. IL-1 beta 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-1 beta 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-1 beta release in both monocytes and macrophages; however, only monocytes also showed P2X7 receptor-independent release of mature IL-1 beta. Furthermore, in monocytes ATP-mediated PS exposure could be activated independently of IL-1 beta production. Release of IL-1 beta from monocytes showed selectivity for specific TLR agonists and was accelerated by P2X7 receptor activation. Human monocytes released more IL-1 beta/cell than macrophages. These data have important implications for inflammatory diseases that involve monocyte activation and IL-1 release.
引用
收藏
页码:23145 / 23156
页数:12
相关论文
共 56 条
  • [51] The use of Toll-like receptor-7 agonist in the treatment of basal cell carcinoma: an overview
    Stockfleth, E
    Trefzer, U
    Garcia-Bartels, C
    Wegner, T
    Schmook, T
    Sterry, W
    [J]. BRITISH JOURNAL OF DERMATOLOGY, 2003, 149 : 53 - 56
  • [52] Pathogen-Induced Interleukin-1β Processing and Secretion Is Regulated by a Biphasic Redox Response
    Tassi, Sara
    Carta, Sonia
    Vene, Roberta
    Delfino, Laura
    Ciriolo, Maria Rosa
    Rubartelli, Anna
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 183 (02) : 1456 - 1462
  • [53] Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor
    Virginio, C
    MacKenzie, A
    North, RA
    Surprenant, A
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1999, 519 (02): : 335 - 346
  • [54] Differential and cell-type specific regulation of responses to Toll-like receptor agonists by ISO-1
    West, Peter W.
    Parker, Lisa C.
    Ward, Jon R.
    Sabroe, Ian
    [J]. IMMUNOLOGY, 2008, 125 (01) : 101 - 110
  • [55] Secretion, of intracellular IL-1 receptor antagonist (type 1) is dependent on P2X7 receptor activation
    Wilson, HL
    Francis, SE
    Dower, SK
    Crossman, DC
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 173 (02) : 1202 - 1208
  • [56] ZOCCHI MR, 2001, FRONTIERS LIFE, P477