ATP-Induced IL-1beta Specific Secretion: True Under Stringent Conditions
SourceFrontiers in Immunology, 6, (2015), article 54
Article / Letter to editor
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Frontiers in Immunology
SubjectRadboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences
Interleukin-1beta is a potent proinflammatory cytokine, of which processing and secretion are tightly regulated. After exposure to various stimuli, mononuclear phagocytes synthesize the inactive precursor (pro-IL-1beta), which is then cleaved intracellularly by caspase-1 and secreted. A widely used method for in vitro secretion of IL-1beta employs LPS-primed human peripheral blood monocytes. Subsequently, adenosine triphosphate (ATP) is added to the cells in order to trigger the P2X7 receptor resulting in processing and secretion of mature IL-1beta. However, it is often reported that secretion is due to cytotoxic effects of ATP with P2X7 receptor-activation-related cell death. We have challenged this concept and demonstrate IL-1beta specific secretion, since there is no increase in cell death and IL-1alpha and IL-18 are not released in the same cultures. More importantly we show that these conclusions can only be drawn under stringent experimental conditions.
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