Article Cell stress increases ATP release in NLRP3 inflammasome-medi...
This view wasconfirmed by the finding that the expression of IL-1β, negligiblein unstimulated monocytes from both healthy donors and CAPSpatients, is induced by LPS at comparable levels (Fig. 1A).Similarly, the baseline expression of NLRP3 was a little higher inCAPS monocytes, but was less induced by LPS than in healthymonocytes (Fig. 1B).To investigate the mechanism underlying the posttranscriptionalincrease of IL-1βsecretion, we compared ATP secretion by mono-cytes from normal subjects and CAPS patients after LPS stimu-lation. As shown in Fig. 1C, CAPS monocytes release levels ofATP dramatically higher (10-fold) than monocytes from healthysubjects. The increase in ATP release was paralleled by increasedsecretion of IL-1β(fivefold; Fig. 1D). LPS-induced ATP release isprevented by the ROS inhibitor DPI (Fig. 1C), indicating thatATP secretion is induced by ROS. Preventing ROS production inmonocytes also prevents the secretion of IL-1β(Fig. 1D)
Fig. 1.Increased levels of IL-1β,IL-18,andIL-1αsecretion by CAPS monocytesdepend on increased release of ATP. (AandB)RT-PCRofIL-1β(A)