positive regulation of pyroptosis

Definition

Target type: biologicalprocess

Any process that increases the frequency, rate or extent of pyroptosis. [PMID:24626226]

Positive regulation of pyroptosis is a crucial cellular process that plays a key role in the innate immune response to pathogens and cellular stress. It is a highly regulated form of programmed cell death characterized by the release of pro-inflammatory cytokines and the formation of pores in the cell membrane, leading to cell lysis and the induction of inflammation.

Here's a detailed description of the biological process:

1. **Activation of Caspase-1:** Pyroptosis is triggered by the activation of caspase-1, a cysteine protease that plays a central role in the inflammatory response. Caspase-1 is activated through the formation of inflammasomes, multiprotein complexes that assemble in response to various danger signals, including microbial components, toxins, and cellular stress.

2. **Inflammasome Assembly:** Inflammasomes are composed of a sensor protein (e.g., NLRP3, NLRC4, AIM2), an adaptor protein (ASC), and pro-caspase-1. When the sensor protein detects a danger signal, it undergoes a conformational change, leading to the recruitment of ASC and pro-caspase-1. This assembly forms the inflammasome, a platform that facilitates the activation of caspase-1.

3. **Caspase-1 Activation and Pro-inflammatory Cytokine Processing:** Activated caspase-1 cleaves and activates pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), which are released from the dying cell. These cytokines contribute to the inflammatory response by recruiting immune cells and promoting the expression of inflammatory genes.

4. **Formation of Membrane Pores and Cell Lysis:** Caspase-1 also cleaves gasdermin D (GSDMD), a protein that forms pores in the cell membrane. GSDMD oligomerizes, creating large pores that disrupt the cell membrane's integrity, leading to the release of cell contents and cell lysis.

5. **Positive Regulation:** The positive regulation of pyroptosis involves mechanisms that enhance or promote the process. These mechanisms can include:

* **Increased expression of inflammasome components:** The expression of inflammasome components, such as NLRP3, ASC, and pro-caspase-1, can be upregulated in response to specific stimuli, enhancing inflammasome formation and caspase-1 activation.

* **Activation of signaling pathways:** Specific signaling pathways, such as the NF-κB pathway, can activate the transcription of genes involved in pyroptosis, leading to increased expression of inflammasome components and pro-inflammatory cytokines.

* **Modulation of cellular environment:** Factors that alter the cellular environment, such as oxidative stress, nutrient deprivation, or mitochondrial dysfunction, can contribute to the activation of pyroptosis by triggering inflammasome assembly and caspase-1 activation.

6. **Significance of Pyroptosis:** Pyroptosis plays a crucial role in innate immunity and host defense against pathogens. It helps to eliminate infected cells and initiate an inflammatory response, promoting the recruitment of immune cells and the clearance of infection. Furthermore, pyroptosis contributes to various inflammatory conditions, such as sepsis, arthritis, and neurodegenerative diseases.

Overall, positive regulation of pyroptosis is a complex and tightly controlled process that involves the activation of caspase-1, the formation of inflammasomes, the processing of pro-inflammatory cytokines, and the formation of membrane pores. It plays a crucial role in the innate immune response and contributes to various physiological and pathological processes.'
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Proteins (1)

Compounds (25)