Interleukin-1 family are secreted

Stable Identifier
R-HSA-449058
Type
Reaction [omitted]
Species
Homo sapiens
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Interleukin-1β (IL-1β) lacks signal sequences for compartmentation within the Golgi and classical secretory vesicles, so release of the mature form to extracellular compartments requires nonclassical mechanisms of secretion which are poorly understood (Eder C 2009; Piccioli P & Rubartelli A 2013). Several secretory pathways were proposed involving secretory lysosomes, exosomes, microvesicles, and autophagic vesicles, possibly through a mechanism similar to chaperone-mediated autophagy (CMA) (Andrei C et al. 2004; Ward JR et al. 2010; MacKenzie A et al. 2001; Gudipaty L et al. 2003; Qu Y et al. 2007; Iula L et al. 2018: reviewed by Eder C 2009; Piccioli P & Rubartelli A 2013; Claude-Taupin A et al. 2018). Further, the route of IL-1β secretion was found to be dependent on the type and strength of the inflammatory stimuli (Semino C et al. 2018; Sitia R & Rubartelli A 2018). Thus, in primary human monocytes small trauma or low pathogen load (LPS) activated a pathway involving secretory lysosomes that allows slow release of IL-1β, followed by apoptotic cell death that switches off the inflammatory response (Semino C et al. 2018). Differently, a stronger stimulus (LRZ) resulted in gasdermin D (GSDMD) 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 (Semino C et al. 2018).

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