Interleukin-1 family are secreted

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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). Caspase-8 and FADD are required for NLRP3 inflammasome activation and IL-1β release (Gurung P et al. 2014, 2016).
Literature References
This event is regulated
Orthologous Events
Cite Us!