ATP-Induced IL-1β Specific Secretion: True Under Stringent Conditions.
Interleukin-1β 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-1β), which is then cleaved intracellularly by caspase-1 and secreted. A widely used method for in vitro secretion of IL-1β 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-1β. 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-1β specific secretion, since there is no increase in cell death and IL-1α 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.
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Monique
M
Stoffels
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Ruben
R
Zaal
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Nina
N
Kok
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Jos W M
JW
van der Meer
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Charles A
CA
Dinarello
Department of Medicine, Radboud University Medical Center, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) , Nijmegen , Netherlands.
Anna
A
Simon
ATP; active secretion; cell death; interleukin-1; stringent experimental conditions