Fig. 7: Routes of IL-1β secretion in human monocytes Two different mechanisms for IL-1β secretion can be activated in primary human monocytes depending on the strength of the inflammatory stimulus. | Cell Death & Disease

Fig. 7: Routes of IL-1β secretion in human monocytes Two different mechanisms for IL-1β secretion can be activated in primary human monocytes depending on the strength of the inflammatory stimulus.

From: Progressive waves of IL-1β release by primary human monocytes via sequential activation of vesicular and gasdermin D-mediated secretory pathways

Fig. 7

a In monocytes from healthy donors (Healthy Mo), small trauma or low pathogen load (LPS) activates a pathway involving secretory lysosomes that allows slow release of IL-1β, followed by apoptotic cell death that switches off the inflammatory response. Differently, a stronger stimulus (LRZ) results in gasdermin D cleavage with generation of the N-terminal domain that assembles in N-rings with formation of pores through which IL-1β can be externalized: this pathway of secretion is followed by pyroptosis, with membrane ruptures through which DAMPs can leave cells, further amplifying the inflammatory response. b Monocytes from CAPS patients (CAPS Mo) contain higher level of ROS at baseline that healthy monocytes. This condition enables the activation of the GSDMD-mediated IL-1β secretory pathway and the consequent hypersecretion of IL-1β even after small trauma or low pathogen load (LPS). Thus, hyperstimulated healthy monocytes and mildly stimulated CAPS monocytes use the same GSDMD-mediated pathway of IL-1β secretion

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