Nigericin

Inflammasome activation with Nigericin

NLRP3 Inflammasome Inducer - Nigericin, sodium salt

Nigericin is a microbial toxin derived from the Gram-positive bacteria Streptomyces hygroscopicus. It induces the release of IL-1β in response to the activation of the NLRP3 (also known as NALP3 or cryopyrin) inflammasome [1]. The NLRP3 inflammasome is a caspase‑1-activating complex comprising the NLR protein NLRP3 and the adaptor ASC required for the maturation and secretion of IL-1β [2].

 More details

Nigericin acts as a potassium ionophore. It probably activates NLRP3 through its ionophore function which allows the intracellular potassium (K+) efflux across the membrane [3]. Whether the formation of non‑selective pannexin-1 pores also contributes to NLRP3 activation upon Nigericin treatment remains unclear [4].

Key features of Nigericin:

• Inducer of the NLRP3 inflammasome
• Potassium ionophore
• Each lot is functionally tested

Read our review on the NLRP3 inflammasome.

Download our Practical guide on Inflammasomes.

References:

1. Mariathasan S. et al., 2006. Cryopyrin activates the inflammasome and ATP. Nature 440;228-32.
2. Martinon F. & Tschopp J., 2004. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell. 117(5):561-74.
3. Muñoz-Planillo R. et al., 2013. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 38(6):1142-53..
4. 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.

Figures

IL-1β production in THP1-Null cells. Human THP-1 monocytes were primed with LPS-EK (1 µg/ml) prior to incubation with increasing concentrations of Nigericin. After 6h and 24h activation, IL-1β secretion was assessed in the culture supernatant using HEK-Blue™ IL-1β sensor cells and the SEAP detection reagent QUANTI-Blue™ Solution. The optical density (OD) was read at 630 nm.

Specifications

Working concentration: 1-10 µM

CAS number: 28643-80-3

Synonym: Antibiotic K178, Polyetherin A

Molecular weight: 746.94 g/mol

Solubility: 5 mg/ml in ethanol

Contents

Nigericin is provided as a sodium salt and is available in two quantities:

• 10 mg : tlrl-nig
• 50 mg : tlrl-nig-5

Nigericin is shipped at room temperature.

Store at -20 °C

Details

The NLRP3 Inflammasome:

The NLRP3 inflammasome is an innate immune sensor that is activated by a two-step process; a first signal (‘priming’) provided mainly by bacterial components or endogenous cytokines involves NF-κB induction, while the second signal provided by a wide array of stimuli including microbial toxins, endogenous molecules or crystalline substances and leads to inflammasome assembly and activation [1, 2].  This triggers inflammasome multimerization and caspase-1 activation with the subsequent cleavage of interleukin-1β (IL-1β)/IL-18 and the pore-forming protein Gasdermin D (GSDMD) into their active forms. Additionally, the activation of the inflammasome also leads to alarmin secretion and pyroptosis, a form of immunogenic cell death.

1. Swanson K.V. et al., 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477.
2. Groslambert M. & Py B. 2018. Spotlight on the NLRP3 inflammasome pathway. J. Inflamm. Res. 11:359.