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Interleukin-1 family are secreted
Stable Identifier
R-HSA-449058
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Disease (Homo sapiens)
Infectious disease (Homo sapiens)
Parasitic Infection Pathways (Homo sapiens)
Leishmania infection (Homo sapiens)
Cell recruitment (pro-inflammatory response) (Homo sapiens)
Purinergic signaling in leishmaniasis infection (Homo sapiens)
Interleukin-1 family are secreted (Homo sapiens)
Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-1 family signaling (Homo sapiens)
Interleukin-1 processing (Homo sapiens)
Interleukin-1 family are secreted (Homo sapiens)
Programmed Cell Death (Homo sapiens)
Regulated Necrosis (Homo sapiens)
Pyroptosis (Homo sapiens)
Interleukin-1 family are secreted (Homo sapiens)
General
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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). Caspase-8 and FADD are required for NLRP3 inflammasome activation and IL-1β release (Gurung P et al. 2014, 2016).
Literature References
PubMed ID
Title
Journal
Year
17641058
Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages
Franchi, L
,
Nunez, G
,
Qu, Y
,
Dubyak, GR
J Immunol
2007
Participants
Input
Interleukin-1 family [cytosol]
(Homo sapiens)
Output
Interleukin-1 family [extracellular region]
(Homo sapiens)
Participates
as an event of
Purinergic signaling in leishmaniasis infection (Homo sapiens)
Pyroptosis (Homo sapiens)
Interleukin-1 processing (Homo sapiens)
This event is regulated
Positively by
Regulator
GSDMD pore complex [plasma membrane]
(Homo sapiens)
Orthologous Events
Interleukin-1 family are secreted (Bos taurus)
Interleukin-1 family are secreted (Canis familiaris)
Interleukin-1 family are secreted (Danio rerio)
Interleukin-1 family are secreted (Gallus gallus)
Interleukin-1 family are secreted (Mus musculus)
Interleukin-1 family are secreted (Rattus norvegicus)
Interleukin-1 family are secreted (Sus scrofa)
Interleukin-1 family are secreted (Xenopus tropicalis)
Authored
Ray, KP (2010-05-17)
Reviewed
D'Eustachio, P (2021-02-17)
Kanneganti, TD (2021-02-17)
Pinteaux, E (2010-09-06)
Shao, F (2021-04-22)
Created
Jupe, S (2009-11-27)
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