Inflammasome research

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This news has been updated in January 2025.

• Unique Antibodies: NLRP3 mAb; Asc pAb; Caspase-1 (p10) mAb; Caspase-1 (p20) mAb
• Potent Activators: Monosodium urate (MSU), Nigericin
• Potent Inhibitors: MCC-950; Isoliquiritigenin; 3-Hydroxybutyric acid; Arglabin and much more

Inflammasome signaling antibodies

Inflammasomes are multi-protein complexes whose activity has been implicated in physiological and pathological inflammation. The hallmarks of inflammasome activation are the secretion of the mature forms of caspase-1 and interleukin-1β (IL-1β) from cells of the innate immune system.

An inflammasome represents a high molecular weight complex that activates inflammatory caspases and cytokines of the IL-1 family (IL-1β, IL-18 and depending on the stimulus also IL-1α). Several inflammasomes have been described which contain different sensor proteins such as NLRP1 (NALP1), NLRP3 (NALP3), IPAF (NLRC4), NLRP6 (NALP6), RIG-I and AIM-2 (absent in melanoma 2). Most of these inflammasomes require the adapter protein Asc (apoptosis-associated specklike protein containing a caspase recruitment domain) to recruit caspase-1 to the inflammasome complex. Upon binding to the inflammasome caspase-1 is cleaved and activated, leading to cleavage of its various targets and causing maturation and secretion of the pro-inflammatory IL-1β. Inflammasomes can be activated through multiple signals including live bacteria, microbial toxins, xeno-compounds, cytoplasmic pathogen-associated molecular patterns (PAMPs) and/or endogenous danger signals (DAMPs).

Inflammasome activity has been causally linked to the induction of numerous inflammatory responses, which can be either beneficial or harmful to the organism. Beneficial responses arise by maintaining homeostatic tissue function (detection and repair of tissue damages after trauma or pathogen invasion). Among the harmful inflammatory responses are particle-induced sterile inflammation, caused by host-derived particles such as monosodium urate (MSU) crystals, which are involved in the pathogenesis of gout, as well as environmental and industrial particles such as asbestos, silica and metallic nanoparticles, which include lung inflammation upon inhalation. Accumulating evidence also implicates inflammasome activity in numerous other diseases, including cancer and the development of metabolic diseases like type 2 diabetes, atherosclerosis and inflammatory bowel diseases. Beneficial effects for the host include the enhancement of vaccine efficacy.

New NLRP3 Inflammasome Starter Sets

Specific caspase-1 detection

Standard inflammasomes signaling antibodies

Inflammasome activators

Inflammasome inhibitors

Inflammasome “priming” activators

Priming of the NLRP3 inflammasome

The most prominent function of the NLRP3 inflammasome is the processing and activation of pro-interleukin-1β (pro-IL-1β). Yet most cells do not express pro-IL-1β and thus prior expression of pro-IL-1β is required. This can be achieved by stimulating receptors such as TLRs (e.g. LPS), NODs or TNF-Rs (e.g. TNF-α) that activate NF-κB and initiate pro-IL-1β transcription. This process of pro-IL-1β induction is called priming (Signal 1). Priming also induces NF-κB-dependent transcription of NLRP3. An additional stimulus (Signal 2) results in the activation of the NLRP3 inflammasome and subsequent initiation of downstream signaling. In the absence of priming, NLRP3 inflammasome-dependent caspase-1 activation can also be observed, but IL-1β secretion is absent.

Inflammasome signaling-related proteins and antibodies

Microtubules & Inflammasome Complex Assembly

Microtubules are cytoskeleton components that are crucial in innate immunity in addition to their general roles in cell division, migration, and morphology. Inflammasomes are assembled from a pattern-recognition receptor, the adapter protein Asc, and caspase-1 to process interleukin-1beta and IL-18 in response to PAMPs or DAMPs. After priming, NLRP3 is expressed and binds to the intracellular membrane of the endoplasmic reticulum and Trans Golgi Network (TGN) and assembles into an oligomeric double-ring cage wrapping the PYD inside, which represents the inactive state. Upon activation, NLRP3 activators induce microtubule polymerization and acetylation. TGN vesicles and NLRP3 are dispersed and further transported to the microtubule-organizing center [MTOC] to engage NEK7 and form the pre-active inflammasome complex (without Asc and pro-Caspase-1) (see AdipoGen’s Inflammasome Wallchart). The released oligomeric inactive NLRP3 cage travels from TGNs to MTOCs along microtubules via the HDAC6-Dynein motor machinery that binds to acetylated α-tubulin. The release of TGN vesicles via microtubules allows NLRP3 to be re-localized in the cytosol closer to mitochondria. As a result, Asc and pro-Caspase-1 molecules on the mitochondria come into close proximity and can interact with NLRP3 to form the active NLRP3 inflammasome complex. As indicated above, the acetylation of α-tubulin is crucial during the NLRP3 activation. As a proposed mechanism, NLRP3 activation leads to mitochondrial dysfunction, leading to the accumulation of acetylated α-tubulin.

Microtubule antibodies

Microtubule inhibitors

Reference

• Samir P, Kesavardhana S, Patmore DM, et al. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature. 2019;573(7775):590-594.