PRE-PRIMING OVERVIEW OF OUTCOMES INFLAMMASOME …
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PRIMING (signal 1) ACTIVATION (signal 2) PRE-PRIMING (for non-canonical inflammasomes) OUTCOMES TLR4 LPS TLR4 LPS IFN-α IFNAR IFN-γ IFNGR Transfected LPS Gram-negave bacteria OMVs (contain LPS) Canonical inflammasome assembly NF-кB Nlrp3 Pro-IL-1β Casp-11/4/5 nucleus Golgi Short (10-60 min) Long (>3 hrs) NEK7 NEK7 Mitochondrial damage K+ K+ K+ Pore-forming agents (Nigericin, ATP) IL-1β/IL-18 secreon Alarmin secreon p50 p65 ASC ASC ASC NLRP3 K + efflux dTGN vesicules Parculate agents (MSU, cholesterol crystals, asbestos) CASP-1 CASP-1 IL-18 IL-18 pro-IL-1β IL-1β pro-IL-18 NT GBPs IRGB10 Release of LPS CASP-11/4/5 TNF-α TNFR IL-1β IL-1R TLR2 Pam3CSK4 Poly(I:C) TLR3 IRF GSDMD NAIPs GBPs IRGB10 Casp-11/4/5 ESCRT Membrane repair Pore formaon Binding phosphoinosides Pore accumulaon ATP IRFs STAT1 IL-1β Transcriponal upregulaon K + NLRP3 Endoplasmic reticulum STAT1 GAS STAT1 STAT1 p50 p65 STAT1 STAT2 IRF9 K + K + GSDMD NT Lysosomal rupture Lysosomal rupture ? primed NLRP3 ox-mtDNA cardiolipin ROS mtDNA mitochondrium ASC ? ? ? Post-translaonal modificaons (PTMs) SENSOR ASC Pro-CASP-1 Cytokine secreon Na+ K+ Non-specific ion fluxes Pro-CASP-1 Pro-CASP-1 HMGB1 LDH IL-1β IL-18 Proteolyc cleavage NT GSDMD NT Proteolyc cleavage pro-CASP-11/4/5 Non-canonical inflammasome assembly K + efflux ? Pyroptosis Plasma membrane rupture Anthrax toxin NLRP1 CARD NLRP3 PAMPs, DAMPs, crystals PYD dsDNA AIM2 PYD NLRC4 NAIP Flagellin, Needle, Rod CARD Pyrin Toxin induced modifications of Rho GTPases PYD Gut-microbiota metabolites LTA NLRP6 PYD PYD NLRP9b DsRNA DHX9 CARD CARD pro-CASP-11 Intracellular LPS pro-CASP-4/5 OVERVIEW OF INFLAMMASOME SENSORS AND ACTIVATORS PYD The TRUSTED SOURCE for all your Inflammasome studies IL-1β/IL-18 Sensor Cells Inflammasome Test Cells Inflammasome Inducers Inflammasome Inhibitors Inflammasome Primers Inflammasome Genes
Transcript of PRE-PRIMING OVERVIEW OF OUTCOMES INFLAMMASOME …
PRIMING (signal 1) ACTIVATION (signal 2)PRE-PRIMING(for non-canonicalinflammasomes)
OUTCOMES
TLR4
LPS
TLR4
LPS IFN-α
IFNAR
IFN-γ
IFNGR
TransfectedLPS
Gram-negativebacteriaOMVs
(contain LPS)
Canonical inflammasomeassembly
NF-кBNlrp3Pro-IL-1βCasp-11/4/5
nucleus
Golgi
Short (10-60 min)Long (>3 hrs)
NEK7
NEK
7
Mitochondrialdamage
K+
K+
K+
Pore-forming agents(Nigericin, ATP)
IL-1β/IL-18secretion
Alarminsecretion
p50 p65
ASC
ASC
ASC
NLR
P3
K+ efflux
dTGNvesicules
Particulate agents(MSU, cholesterol crystals,asbestos)
CASP-1
CASP-1IL-18
IL-18pro-IL-1β
IL-1β
pro-IL-18
NT
GBPsIRGB10
Releaseof LPS
CASP-11/4/5
TNF-α
TNFR
IL-1β
IL-1R TLR2
Pam3CSK4Poly(I:C)
TLR3
IRF
GSDMDNAIPsGBPsIRGB10Casp-11/4/5
ESCRT
Membranerepair
Poreformation
Bindingphosphoinositides
Poreaccumulation
ATP
IRFs
STAT1
IL-1β
Transcriptionalupregulation
K+
NLRP3
Endoplasmicreticulum
STAT1GAS
STAT1STAT1p50 p65
STAT1STAT2
IRF9
K+
K+
GSDMDNT
LysosomalruptureLysosomal
rupture
?
primed
NLRP3
ox-mtDNA
cardiolipin
ROS
mtDNA
mitochondrium
ASC
?
?
?
Post-translationalmodifications (PTMs)
SENSORASC
Pro-CASP-1
Cytokine secretion
Na+K+
Non-specificion fluxes
Pro-CASP-1
Pro-CASP-1
HMGB1LDHIL-1β IL-18
Proteolyticcleavage
NTGSDMD
NT Proteolyticcleavage
pro-CASP-11/4/5
Non-canonicalinflammasome
assembly
K+ efflux
?
Pyroptosis
Plasma membranerupture
Anthrax toxin
NLRP1
CARD
NLRP3
PAMPs, DAMPs, crystals
PYD
dsDNA
AIM2
PYD
NLRC4
NAIP
Flagellin, Needle,Rod
CARD
Pyrin
Toxin induced modifications of Rho GTPases
PYD
Gut-microbiotametabolites LTA
NLRP6
PYD
PYDNLRP9b
DsRNA
DHX9
CARD
CARD pro-CASP-11
Intracellular LPS
pro-CASP-4/5
OVERVIEW OFINFLAMMASOME SENSORS
AND ACTIVATORS
PYD
The TRUSTED SOURCE for all your Inflammasome studiesIL-1β/IL-18 Sensor CellsInflammasome Test CellsInflammasome Inducers
Inflammasome InhibitorsInflammasome PrimersInflammasome Genes
