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NRLP3 inflammasome

ATP
Nigericin
Crystals: MSU, CPPD
Vaccine adjuvant: Alum

AIM2 inflammasome

poly(dA:dT)

Inflammasome Inhibitors
HEK-Blue™ IL-1β Cells

Product Lines > Toll-Like Receptors > TLR Ligands > Inflammasome Inducers

Inflammasome Inducers

The inflammasome is a multiprotein complex that induces the activation of caspase-1 and the subsequent maturation of interleukin-1β. Several inflammasomes have been identified such as the NLRP3 (NALP3) inflammasome and the AIM2 inflammasome.

Inflammasome is activated by a large variety of microbial molecules, danger signals and crystalline substances.
InvivoGen provides a selection of these molecules known to induce the assembly of the NLRP3 and AIM2 inflammasomes.

NLRP3 Inflammasome Inducers :
- ATP
- Nigericin
- Crystals: MSU, CPPD
- Vaccine adjuvant: Alum

AIM2 Inflammasome Inducer :
- poly(dA:dT)

All inflammasome inducers provided by InvivoGen have been endotoxin-tested and validated in house using the THP-1/HEK-Blue™-IL-1β assay.
Each product is provided as a solid and shipped at room temperature. Store at room temperature, 4°C or -20°C according to the product label.

IL-1β secretion by inflammasome inducers.

THP1 cells pretreated with PMA and primed with LPS (1 μg/ml) were stimulated with ATP (5 mM), nigericin (1 μM), alum (200 μg/ml), MSU (200 μg/ml) or CPPD (200 μg/ml).
After 24h incubation, THP-1 supernatants were added to HEK-Blue™ IL-1β cells. IL-1β-induced NF-κB activation was assessed by measuring the levels of SEAP in the supernatant of HEK-Blue™ IL-1β cells using the QUANTI-Blue™ assay.

NRLP3 inflammasome

ATP

Adenosine triphosphate (ATP), a potassium efflux agent, can trigger the activation of NALP3 inflammasome in response to PAMPs, such as LPS and peptidoglycan.
It stimulates the caspase-1-dependent cleavage and secretion of IL-1β from LPS-stimulated cells [1]. ATP triggers the opening of the nonselective cation channel of the purinergic P2X₇ receptor, followed by the gradual opening of a larger pore. The larger pore is attributed to pannexin-1, which is recruited upon P2X₇ receptor activation [2]. Activation of the P2X₇ receptor results in potassium efflux which is necessary for activation of the posttranslational maturation of IL-1β [3].

1. Mariathasan S. et al., 2006. Cryopyrin activates the inflammasome and ATP. Nature 440;228-32.
2. Locovei S. et al., 2007. Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett. 581(3):483-8.
3. Perregaux D. & Gabel CA., 1994. Interleukin-1b maturation and release in response to ATP and nigericin. J Biol. Chem. 269:15195-15203.

Product	Description	Working Conc.	TDS	MSDS	Qty	Cat. Code	Price	Order
ATP	Adenosine 5'-triphosphate disodium salt	5 mM	PDF	PDF	1 g	tlrl-atp	check

Nigericin

Nigericin is a microbial toxin derived from Streptomyces hygroscopicus. Nigericin acts as a potassium ionophore. The release of IL-1β in response to nigericin has been demonstrated to be NALP3-dependent [1].

Similar to ATP, nigericin induces a net decrease in intracellular levels of potassium which is crucial for the activation of caspase-1 [2]. Nigericin requires signaling through pannexin-1 to induce caspase-1 maturation and IL-1β processing and release [3].

1. Mariathasan S. et al., 2006. Cryopyrin activates the inflammasome and ATP. Nature 440;228-32.
2. Locovei S. et al., 2007. Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett. 581(3):483-8.
3. Pelegrin P, & Surprenant A., 2007. Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem. 282(4):2386-94.

Product	Description	Working Conc.	TDS	MSDS	Qty	Cat. Code	Price	Order
Nigericin	Nigericin, sodium salt	1 µM	PDF	PDF	10 mg	tlrl-nig	check
Nigericin	Nigericin, sodium salt	1 µM	PDF	PDF	50 mg	tlrl-nig-5	check

Crystals: MSU, CPPD

Crystals of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) are the aetiological agents of the inflammatory joint diseases gout and pseudo-gout, respectively.
Both pathogenic crystals have been recently shown to be potent activators of caspase-1 through the NLRP3 inflammasome [1]. Involvement of the inflammasome is suggested by the finding that macrophages from mice deficient in various components of the inflammasome are defective in crystal-induced IL-1β induction [1].
The mechanism leading to the NLRP3 inflammasome activation is still poorly understood, but it may involve phagocytosis of the crystals and generation of reactive oxygen species.

1. Martinon F. et al., 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature.440(7081):237-41.

Product	Description	Working Conc.	TDS	MSDS	Qty	Cat. Code	Price	Order
MSU Crystals	Monosodium Urate Crystals	50 - 200 µg/ml	PDF	PDF	5 mg	tlrl-msu	check
CPPD crystals	Calcium Pyrophosphate Dihydrate crystals	50 - 200 µg/ml	PDF	PDF	5 mg	tlrl-cppd	check

Vaccine adjuvant: Alum

Aluminum hydroxide and potassium salts (alum) are commonly used vaccine adjuvants. Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect.

Alum has been demonstrated to activate caspase-1 and triggers IL-1β and IL-18 secretion [1]. All alum preparations contain crystals. The alum-induced release of IL-1β in macrophages is dependent on NALP3 and ASC, indicating that alum triggers inflammation through activation of the NALP3 inflammasome [2]. Alum has been shown to trigger NALP3 activation through lysosomal destabilization [2].

1. Li H. et al., 2008. Cutting Edge: Inflammasome activation by Alum and Alum’s adjuvant effect are mediated by NLRP3. J Immunol. 181:17-21.
2. Hornung V. et al., 2008. Silica crystals and aluminium salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9:847-856

Product	Description	Working Conc.	TDS	MSDS	Qty	Cat. Code	Price	Order
Alum Crystals	Aluminium potassium sulfate	10 - 200 µg/ml	PDF	PDF	1 g	tlrl-alk	check

AIM2 inflammasome

Double-stranded DNA: poly(dA:dT)

Poly(dA:dT) is a repetitive synthetic double-stranded DNA sequence of poly(dA-dT)•poly(dT-dA). Poly(dA:dT) is complexed with the cationic lipid LyoVec™ to facilitate its uptake.
Transfection of macrophages with poly(dA:dT) leads to the production of IL-1β [1]. This response to transfected poly(dA:dT) is ASC-dependent, but NALP3 independent. AIM2 was recently shown to sense poly(dA:dT), form an inflammasome with ASC and trigger caspase-1 activation [2, 3, 4]. Poly(dA:dT) binds to AIM2 and induces its oligomerization, which is the first demonstration of an inflammasome bound to its ligand [2].

1. Muruve DA. et al., 2008. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature. 452(7183):103-7.
2. Hornung V. et al., 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 458(7237):514-8..
3. Fernandes-Alnemri T. et al., 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 458(7237):509-13.
4. Bürckstümmer T. et al., 2008. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 10(3):266-72

Product	Description	Working Conc.	TDS	MSDS	Qty	Cat. Code	Price	Order
Poly(dA:dT), double-stranded B DNA	poly(dA-dT)•poly(dT-dA)/LyoVec complexes	1-5 µg/ml	PDF	PDF	100 µg	tlrl-pat	check

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Note that the sequence of available ORFs provided by InvivoGen can differ from a given reference Genbank record due to genetic variations and/or alternative splicing. Customers should verify that the version of a gene sold by InvivoGen is suitable for the customer needs.

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