scaricalo in formato PDF - labogen srl
scaricalo in formato PDF - labogen srl
scaricalo in formato PDF - labogen srl
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
INNATE IMMUNITY 3<br />
Inflammasome Inducers & Inhibitors<br />
The <strong>in</strong>flammasome is a multi-prote<strong>in</strong> complex <strong>in</strong>volved <strong>in</strong> the production of mature IL-1b. It is activated by a large variety of microbial molecules,<br />
danger signals and crystall<strong>in</strong>e substances. InvivoGen provides a selection of these molecules known to <strong>in</strong>duce the assembly of the NLRP3 or<br />
AIM2 <strong>in</strong>flammasomes. We also offer some <strong>in</strong>hibitors to confirm the ability of a given molecule to activate the <strong>in</strong>flammasome or to test the<br />
importance of phagocytosis or potassium efflux <strong>in</strong> this process. These <strong>in</strong>flammasome <strong>in</strong>ducers and <strong>in</strong>hibitors have been validated us<strong>in</strong>g the<br />
THP-1/HEK-Blue -IL-1b Assay (see page 100).<br />
98<br />
PRODUCT DESCRIPTION<br />
Inflammasome Inducers<br />
Alum Crystals Alum<strong>in</strong>ium potassium sulfate 10 - 200 μg/ml 1 g tlrl-alk<br />
ATP Adenos<strong>in</strong>e 5′-triphosphate disodium salt 5 mM 1 g tlrl-atp<br />
CPPD Crystals Calcium pyrophosphate dihydrate 50 - 200 μg/ml 5 mg tlrl-cppd<br />
Hemozo<strong>in</strong> NEW Synthetic heme crystal 50 - 400 μg/ml 5 mg tlrl-hz<br />
MSU Crystals Monosodium urate (uric acid) 50 - 200 μg/ml 5 mg tlrl-msu<br />
Nigeric<strong>in</strong> Nigeric<strong>in</strong>, sodium salt 1 μM 10 mg tlrl-nig<br />
Poly(dA:dT), double-stranded B DNA Poly(dA-dT)•poly(dT-dA)/LyoVec complex 1 - 5 μg/ml 100 μg tlrl-pat<br />
Inflammasome Inhibitors<br />
Inflammasome Inducers<br />
Alum Crystals - NLRP3 Inflammasome Inducer<br />
Alum<strong>in</strong>um hydroxide and potassium salts (alum) are commonly used vacc<strong>in</strong>e adjuvants. Adjuvants are vacc<strong>in</strong>e additives that stimulate the immune system<br />
without hav<strong>in</strong>g any specific antigenic effect. Alum has been demonstrated to activate caspase-1 and triggers IL-1b and IL-18 secretion 1 . All alum preparations<br />
conta<strong>in</strong> crystals. The alum-<strong>in</strong>duced release of IL-1b <strong>in</strong> macrophages is dependent on NLRP3 and ASC, <strong>in</strong>dicat<strong>in</strong>g that alum triggers <strong>in</strong>flammation through<br />
activation of the NLRP3 <strong>in</strong>flammasome 2 . Alum has been shown to trigger NLRP3 activation through lysosomal destabilization 2 .<br />
ATP - NLRP3 Inflammasome Inducer<br />
Adenos<strong>in</strong>e triphosphate (ATP), a potassium efflux agent, can trigger the activation of NLRP3 <strong>in</strong>flammasome <strong>in</strong> response to PAMPs, such as LPS and<br />
peptidoglycan. It stimulates the caspase-1-dependent cleavage and secretion of IL-1b from LPS-stimulated cells 3 . ATP triggers the open<strong>in</strong>g of the nonselective<br />
cation channel of the pur<strong>in</strong>ergic P2X7 receptor, followed by the gradual open<strong>in</strong>g of a larger pore. The larger pore is attributed to pannex<strong>in</strong>-1, which<br />
is recruited upon P2X7 receptor activation 4 . Activation of the P2X7 receptor results <strong>in</strong> potassium efflux which is necessary for activation of the posttranslational<br />
maturation of IL-1b 5 .<br />
Hemozo<strong>in</strong> - NLRP3 Inflammasome Inducer NEW<br />
Hemozo<strong>in</strong> is a dark-brown heme crystal produced by the <strong>in</strong>traerythrocytic parasite Plasmodium, the causative agent of malaria. Hemozo<strong>in</strong> is taken up by<br />
macrophages <strong>in</strong>itiat<strong>in</strong>g signals that lead to the production of IL-1b. Hemozo<strong>in</strong>-<strong>in</strong>duced IL-1b production is dependent on the activation of the NLRP3<br />
<strong>in</strong>flammasome 6, 7 . Synthetic hemozo<strong>in</strong> has been shown to possess adjuvant properties that differ depend<strong>in</strong>g on the method of synthesis 8 . InvivoGen provides<br />
a chemically synthesized hemozo<strong>in</strong> us<strong>in</strong>g an acidic method.<br />
MSU & CPPD Crystals - NLRP3 Inflammasome Inducers<br />
Crystals of monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) are the aetiological agents of the <strong>in</strong>flammatory jo<strong>in</strong>t diseases gout<br />
and pseudo-gout, respectively. Both pathogenic crystals have been recently shown to be potent activators of caspase-1 through the NLRP3 <strong>in</strong>flammasome 9 .<br />
Involvement of the <strong>in</strong>flammasome is suggested by the f<strong>in</strong>d<strong>in</strong>g that macrophages from mice deficient <strong>in</strong> various components of the <strong>in</strong>flammasome are<br />
defective <strong>in</strong> crystal-<strong>in</strong>duced IL-1b <strong>in</strong>duction. NLRP3 activation requires the phagocytosis of crystals that leads to lysosomal damage which appears to be<br />
the signal recognized by the <strong>in</strong>flammasome result<strong>in</strong>g <strong>in</strong> its activation 2 .<br />
www.<strong>in</strong>vivogen.com/<strong>in</strong>flammasome<br />
WORKING<br />
CONCENTRATION<br />
QUANTITY CATALOG<br />
CODE<br />
Glybenclamide Proton pump <strong>in</strong>hibitor 25 μg/ml 1 g tlrl-gly<br />
Z-VAD-FMK Pan-caspase Inhibitor 10 μg/ml (20 μM) 1 mg tlrl-vad