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Apoptosis : An International Journal on... Feb 2022Pyroptosis is a newly discovered form of programmed cell death mediated by the gasdermin protein, that is accompanied by inflammation and immune response. A growing body... (Review)
Review
Pyroptosis is a newly discovered form of programmed cell death mediated by the gasdermin protein, that is accompanied by inflammation and immune response. A growing body of evidence suggests that pyroptosis is closely related to cancer, and it is becoming a new cancer research topic. Studies have suggested that different cancer cells activate pyroptosis in different ways and that the effects of pyroptosis vary in different cancer backgrounds. In this article, we briefly introduce the definition, characteristics, and activation pathways of pyroptosis. Then we review the complex effects of pyroptosis on cancer development, which generally include inhibition of cancer cell viability, impacts on the invasion and migration of cancer cells, improvement of antitumor immunity, and enhancement of chemotherapy sensitivity. We also discuss drugs and compounds that can induce pyroptosis, as well as the interaction between pyroptosis and apoptosis. Elucidating the mechanisms of the complex effects of pyroptosis is likely to pave the way for therapeutic approaches for cancer in the future.
Topics: Apoptosis; Humans; Inflammation; Neoplasms; Pyroptosis
PubMed: 35064425
DOI: 10.1007/s10495-021-01703-y -
Journal of Molecular Biology Feb 2022Programmed cell deaths are pathways involving cells playing an active role in their own destruction. Depending on the signaling system of the process, programmed cell... (Review)
Review
Programmed cell deaths are pathways involving cells playing an active role in their own destruction. Depending on the signaling system of the process, programmed cell death can be divided into two categories, pro-inflammatory and non-inflammatory. Pyroptosis is a pro-inflammatory form of programmed cell death. Upon cell death, a plethora of cytokines are released and trigger a cascade of responses from the neighboring cells. The pyroptosis process is a double-edged sword, could be both beneficial and detrimental in various inflammatory disorders and disease conditions. A physiological outcome of these responses is tissue damage, and sometimes death of the host. In this review, we focus on the inflammatory response triggered by pyroptosis, and resulting tissue damage in selected organs.
Topics: Apoptosis; Cytokines; Humans; Inflammasomes; Inflammation; Pyroptosis
PubMed: 34653436
DOI: 10.1016/j.jmb.2021.167301 -
Journal of Clinical Periodontology Oct 2021Pyroptosis and inflamm-aging have been newly identified to be involved in diabetic periodontitis. This study aimed to elucidate whether macrophage pyroptosis plays a...
AIM
Pyroptosis and inflamm-aging have been newly identified to be involved in diabetic periodontitis. This study aimed to elucidate whether macrophage pyroptosis plays a role in periodontal inflamm-aging by impacting the senescence of fibroblasts, as well as the potential mechanism via NLR family CARD domain-containing protein 4 (NLRC4) phosphorylation.
MATERIALS AND METHODS
Diabetes was induced in mice using streptozotocin. Periodontal pyroptosis and senescence were detected using immunohistochemical analysis. Prior to evaluating senescence in human gingival fibroblasts cultured with conditioned medium derived from macrophages, RAW 264.7 macrophages were confirmed to undergo pyroptosis by scanning electron microscopy and gasdermin D (GSDMD) detection. The NLRC4-related pathway was examined under hyperglycaemic conditions.
RESULTS
Our data showed that macrophage pyroptosis induced the expression of senescent markers in vivo and in vitro. Importantly, clearance of pyroptotic macrophages rescued senescence in fibroblasts. Furthermore, GSDMD activation and pyroptosis in hyperglycaemia were found to be mediated by NLRC4 phosphorylation.
CONCLUSIONS
Hyperglycaemia could initially induce macrophage pyroptosis and lead to cellular senescence, thereby critically contributing to periodontal pathogenesis in diabetes. In particular, NLRC4 phosphorylation could be a potential therapeutic target for the inhibition of this process.
Topics: Aging; Animals; Diabetes Mellitus; Hyperglycemia; Macrophages; Mice; Pyroptosis
PubMed: 34219262
DOI: 10.1111/jcpe.13517 -
Journal of Experimental & Clinical... May 2021Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell... (Review)
Review
BACKGROUND
Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.
MAIN BODY
Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.
CONCLUSION
In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.
Topics: Animals; Cell Death; Humans; Mice; Neoplasms; Pyroptosis; Tumor Microenvironment
PubMed: 33941231
DOI: 10.1186/s13046-021-01959-x -
Life Sciences Nov 2022Pyroptosis represents an inflammatory cell death form induced by inflammasomes and performed by gasdermins. It is characterized by swelling, pore formation, release of... (Review)
Review
Pyroptosis represents an inflammatory cell death form induced by inflammasomes and performed by gasdermins. It is characterized by swelling, pore formation, release of cellular content and the activation of innate immunity leading to inflammation. Hence, pyroptosis contributes to inflammatory conditions like cancer and has emerged as a promising immuno-strategy for treating cancer. The advent of nanotechnology, which overlaps with the discovery of pyroptotic cell death, has enabled the development of nano-based pyroptosis inducing platforms aimed at overcoming resistance to apoptosis and enhancing tumor immunity. In this paper, we will describe the various molecular pathways underlying pyroptosis, such as canonical and non-canonical pyroptosis. We will then explore the advances in the field of pyroptosis-based nanotherapeutics and their future implications.
Topics: Apoptosis; Cell Death; Humans; Inflammasomes; Inflammation; Neoplasms; Pyroptosis
PubMed: 36115581
DOI: 10.1016/j.lfs.2022.120970 -
Biomedicine & Pharmacotherapy =... Oct 2023Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin protein-mediated membrane pore formation, cell swelling, and rapid lysis.... (Review)
Review
Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin protein-mediated membrane pore formation, cell swelling, and rapid lysis. Recent studies have suggested that pyroptosis is closely related to atherosclerosis (AS). Previous studies reported that pyroptosis involving endothelial cells (ECs), macrophages, and smooth muscle cells (SMCs) plays an important role in the formation and development of AS. Pyroptosis not only causes local inflammation but also amplifies the inflammatory response and it aggravates plaque instability, leading to plaque rupture and thrombosis, eventually resulting in acute cardiovascular events. In this review, we clarified some novel pathways and mechanics and presented some potential drugs.
Topics: Humans; Pyroptosis; Endothelial Cells; Atherosclerosis; Cell Death; Inflammation
PubMed: 37643484
DOI: 10.1016/j.biopha.2023.115369 -
Physiological Research Mar 2023Pyroptosis is a form of cell death associated with inflammation. In the maintenance of airway homeostasis, pyroptosis goes through activation and assembly of... (Review)
Review
Pyroptosis is a form of cell death associated with inflammation. In the maintenance of airway homeostasis, pyroptosis goes through activation and assembly of Inflammasome. The pyroptosis pathway is mediated by caspase which activates the pore-forming effect of substrate gasdermin family members. It eventually leads to lysis and release of the cell contents and then induces an inflammatory response. In this process, it participates in airway homeostasis regulation by affecting airway immunity, airway epithelial structure and airway microbiota. Therefore, we discussed the correlation between airway immunity, airway epithelial structure, airway microbiota and the mechanism of pyroptosis to describe the role of pyroptosis in airway homeostasis regulation which is of great significance for understanding the occurrence and treatment of airway inflammatory diseases.
Topics: Humans; Pyroptosis; Inflammasomes; Caspases; Inflammation; Homeostasis
PubMed: 36545873
DOI: 10.33549/physiolres.934971 -
Molecular Biology Reports Dec 2023Pyroptosis is a gasdermins-mediated programmed cell death that plays an essential role in immune regulation, and its role in autoimmune disease and cancer has been... (Review)
Review
Pyroptosis is a gasdermins-mediated programmed cell death that plays an essential role in immune regulation, and its role in autoimmune disease and cancer has been studied extensively. Increasing evidence shows that various microbial infections can lead to pyroptosis, associated with the occurrence and development of microbial infectious diseases. This study reviews the recent advances in pyroptosis in microbial infection, including bacterial, viral, and fungal infections. We also explore potential therapeutic strategies for treating microbial infection-related diseases by targeting pyroptosis.
Topics: Humans; Pyroptosis; Inflammasomes; Apoptosis; Neoplasms
PubMed: 38158461
DOI: 10.1007/s11033-023-09078-w -
Immunological Reviews Mar 2023Pyroptosis is a proinflammatory mode of lytic cell death mediated by accumulation of plasma membrane (PM) macropores composed of gasdermin-family (GSDM) proteins. It... (Review)
Review
Pyroptosis is a proinflammatory mode of lytic cell death mediated by accumulation of plasma membrane (PM) macropores composed of gasdermin-family (GSDM) proteins. It facilitates two major functions in innate immunity: (i) elimination of intracellular replicative niches for pathogenic bacteria; and (ii) non-classical secretion of IL-1 family cytokines that amplify host-beneficial inflammatory responses to microbial infection or tissue damage. Physiological roles for gasdermin D (GSDMD) in pyroptosis and IL-1β release during inflammasome signaling have been extensively characterized in macrophages. This involves cleavage of GSDMD by caspase-1 to generate GSDMD macropores that mediate IL-1β efflux and progression to pyroptotic lysis. Neutrophils, which rapidly accumulate in large numbers at sites of tissue infection or damage, become the predominant local source of IL-1β in coordination with their potent microbiocidal capacity. Similar to macrophages, neutrophils express GSDMD and utilize the same spectrum of diverse inflammasome platforms for caspase-1-mediated cleavage of GSDMD. Distinct from macrophages, neutrophils possess a remarkable capacity to resist progression to GSDMD-dependent pyroptotic lysis to preserve their viability for efficient microbial killing while maintaining GSDMD-dependent mechanisms for export of bioactive IL-1β. Rather, neutrophils employ cell-specific mechanisms to conditionally engage GSDMD-mediated pyroptosis in response to bacterial pathogens that use neutrophils as replicative niches. GSDMD and pyroptosis have also been mechanistically linked to induction of NETosis, a signature neutrophil pathway that expels decondensed nuclear DNA into extracellular compartments for immobilization and killing of microbial pathogens. This review summarizes a rapidly growing number of recent studies that have produced new insights, unexpected mechanistic nuances, and some controversies regarding the regulation of, and roles for, neutrophil inflammasomes, pyroptosis, and GSDMs in diverse innate immune responses.
Topics: Humans; Pyroptosis; Inflammasomes; Neutrophils; Intracellular Signaling Peptides and Proteins; Gasdermins; Caspase 1; Signal Transduction
PubMed: 36656082
DOI: 10.1111/imr.13186 -
Clinica Chimica Acta; International... Jun 2022Pyroptosis is identified as a pro-inflammatory programmed cell death, mediated by gasdermins (GSDMs) family of proteins accompanied by pro-inflammatory signals release.... (Review)
Review
Pyroptosis is identified as a pro-inflammatory programmed cell death, mediated by gasdermins (GSDMs) family of proteins accompanied by pro-inflammatory signals release. As essential players in innate immunity, inflammasomes are intracellular protein complexes which cleave gasdermin D (GSDMD), forming structurally stable pores in the cell membrane, subsequently inducing pyroptosis. Extensive evidence indicates that inflammasomes and pyroptosis contributes to tumors, nerve injury, inflammatory diseases and metabolic disorders. As a metabolic disorder, diabetes is characterized with hyperglycemia, insulin resistance and chronic inflammation. Meanwhile, aberrant pyroptosis exerts a key role in the occurrence and progression of diabetes and its common complication, diabetic nephropathy (DN). Furthermore, evidence has shown that DN patients and animal models exhibit increased circulating IL-1β and inflammasome, while decreasing the expression of key components of the inflammasome mitigates kidney damage and delays progression. Current research has reported that non-coding RNAs (ncRNAs) are involved in activation of inflammasomes and play a crucial role in the control of pyroptosis in DN pathogenesis. In addition, studies have indicated that some natural plant compounds have therapeutic potential via regulation of inflammasomes and pyroptosis to prevent and potentially treat DN. This mini-review examines the molecular mechanism of inflammasome activation and pyroptosis, highlights the critical roles of ncRNA and explores potential therapeutics to regulate pyroptosis in DN.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Humans; Inflammasomes; Inflammation; Phosphate-Binding Proteins; Pyroptosis
PubMed: 35427562
DOI: 10.1016/j.cca.2022.04.011