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

ABSTRACT: IL-1β is an essential cytokine, but its release needs to be strictly controlled to avoid severe inflammatory manifestations. Lacking a signal sequence, IL-1β does not follow the endoplasmic reticulum-Golgi route. Several pathways have been proposed to mediate its release. One involves the translocation of pro-IL-1β into intracellular vesicles of lysosomal origin that eventually fuse with the plasma membrane. Another exploits pores formed on the plasma membrane upon proteolytic cleavage of gasdermin D (GSDMD). Here we investigated how primary monocytes-the main source of IL-1β in humans-control IL-1β release in response to pro-inflammatory stimuli of increasing intensity and found that two different routes are induced depending on the strength of activation. Triggering of Toll-like receptor

SUBMITTER: Semino C 

PROVIDER: S-EPMC6199333 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature