Cholesterol Crystals - NLRP3 Inflammasome Inducer

CAS number 57-88-5

SPECIFICATIONS

Specifications

Synonyms
3S,8S,9S,10R,13R,14S,17R)-10,13-diméthyl-17[(2R)-6-méthylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17dodécahydro-1H-cyclopenta[a]phénanthren-3-ol
Target

NLRP3

CAS number
57-88-5
Chemical formula

C27H46O

Molecular weight
386.66 g/mol
Working concentration

20 mg/ml in sterile water

Solubility

Not soluble

Appearance (form)
Dried powder
Endotoxin

Negative (tested using EndotoxDetect™ assay)

Tested applications

Induction of NLRP3 inflammasome response

Applications

NLRP3 activation

Quality control

Each lot is functionally tested and validated.

CONTENTS

Contents

  • Product: 
    Cholesterol Crystals
  • Cat code: 
    tlrl-chol
  • Quantity: 
    20 mg

Shipping & Storage

  • Shipping method:  Room temperature
  • Storage:

    • -20 °C
    Stability: - 20°C for up to 1 year

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

Atherosclerosis

Atherosclerosis is a progressive chronic disease characterized by the accumulation of lipid, and cholesterol crystals (CCs), and infiltration of immune cells, such as monocytes, macrophages, T cells, and neutrophils [1]. During atherogenesis, cholesterol precipitates and crystallizes into CCs in the arterial wall. Phagocytosis of these sharp-edged CCs causes lysosomal damage, sensed by the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. This leads to the release of pro-inflammatory cytokines (e.g. interleukin 1β (IL-1β), which is associated with disease severity and outcome [1].

NLRP3

The NLRP3 inflammasome is an intracellular multi-protein complex that plays a central role in innate immunity. It is activated by a two-step process. A first signal (‘priming’) is provided by pathogen-associated molecular patterns (PAMPs) or cytokines. It allows the transcriptional upregulation of key inflammasome actors and the post-translational modification of NLRP3. A wide array of stimuli including microbial toxins, endogenous molecules or crystalline substances provides the second signal (‘activation’). The current paradigm is that NLRP3 does not bind directly to these molecules. Rather it senses downstream cytosolic stress signals such as K+ efflux. This triggers inflammasome multimerization and pro-caspase-1 maturation. Proximity-induced autolytic activation of caspase-1 leads to the formation of gasdermin D (GSDMD) pores at the cell surface, allowing IL-1β/IL-18 and alarmin secretion, and ultimately, pyroptosis [3,4].

 

References:

1. Niyonzima N, et al., 2020. Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis. EBioMedicine.;60:102985.
2. 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.
3. Swanson K.V. et al., 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477.
4. Groslambert M. & Py B. 2018. Spotlight on the NLRP3 inflammasome pathway. J. Inflamm. Res. 11:359.

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