An Introduction to Pyroptosis!

An Introduction to Pyroptosis!

In this excerpt, we will give an overview of Pyroptosis and its dependency on Caspase-1.  Be sure to read the full article in our educational materials.

Pyroptosis is a form of inflammatory programmed cell death, triggered by various pathological stimuli such as stroke, heart attack, cancer, and microbial infections. Other known types of programmed cell death include apoptosis and necroptosis. Pyroptosis is fundamentally distinct from other cell death pathways by its exclusive dependency on caspase-1. 

Pyroptosis promotes the rapid clearance of various bacterial and viral infections by removing intracellular replication niches and by enhancing the host’s defensive response. Cells can use a broad range of intracellular and extracellular mechanisms for detecting different “danger” signals generated or released during infection or injury. These detection mechanisms typically involve pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and Absent in melanoma 2 (AIM2) like receptors (ALRs), to name a few. PRRs initiate a signaling cascade that leads to activation and production of inflammatory cytokines upon recognition of conserved microbial signatures or danger signals (commonly referred to as pathogen associated molecular patterns or PAMPs, or danger associated molecular patterns or DAMPS, respectively). Recognition of PAMPs, DAMPs, and some foreign toxins can lead to inflammasome activation, which triggers activation of caspase-1, and the initiation of pyroptosis. In addition to promoting an immune response, activation of the inflammasome also leads to an increase in pyroptotic cell death. 

Pyroptosis acts as a defense mechanism against infection by inducing inflammation. The formation of inflammasomes and the activity of caspase-1 determine the balance between eradication of the pathogen-associated disease state versus coping with a protracted infection. In a healthy cell, caspase-1 activation helps to fight infection. 

Highly conserved cell death processes such as pyroptosis can and will function as a double edge sword. Inflammasome activation results in an increase in cytokine levels, which will augment the consequences of inflammation. This in turn, contributes to the development of the adaptive immune response as infection progresses. The ultimate resolution will clear pathogens. In contrast, persistent inflammation has also been linked to a variety of autoimmune and autoinflammatory diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, atherosclerosis, type 2 diabetes, and obesity. If the amplification cycles persist, metabolic disorder, auto-inflammatory diseases and liver injury associated with chronic inflammation will take place. Since pyroptosis is involved in many beneficial and detrimental inflammatory processes, this conserved cell death process remains an important area of continued study.

Learn About Our Pyroptosis Kits

• ICT’s Pyroptosis/Caspase-1 Assay Kit utilizes our popular FLICA® technology to detect caspase-1 activation.
• These kits contains the caspase-1 inhibitor reagents, which have the preferred binding sequence for caspase-1, Tyr-Val-Ala-Asp (YVAD).
• These kits also contains Nigericin, a potent microbial toxin derived from 
Streptomyces hygroscopicus, that acts as a potassium ionophore, capable of inducing a net decrease in intracellular levels of potassium which is crucial for oligomerization of the NLRP3 inflammasome and activation of caspase-1. Nigericin is included in this kit as a positive control. It has been shown to generate a robust caspase-1 activation response in various cell lines

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