DNA Sensing in the Innate Immune Response DOI Open Access
Benoit Briard, David E. Place, Thirumala‐Devi Kanneganti

et al.

Physiology, Journal Year: 2020, Volume and Issue: 35(2), P. 112 - 124

Published: Feb. 6, 2020

The innate immune system recognizes conserved pathogen-associated molecular patterns and produces inflammatory cytokines that direct downstream responses. inappropriate localization of DNA within the cell cytosol or endosomal compartments indicates a may either be infected by virus bacterium, has problems with its own nuclear integrity. This is sensed certain receptors mediate cytokine production and, in some cases, initiate an lytic form death called pyroptosis. Dysregulation these DNA-sensing pathways thought to contribute autoimmune diseases development cancer. In this review, we will discuss sensors Toll-like receptor 9 (TLR9), cyclic GMP-AMP synthase (cGAS), stimulator interferon genes (STING), absent melanoma 2 (AIM2), gamma-inducible 16 (IFI16), their ligands, physiological significance. We also examine less-well-understood DEAH- DEAD-box helicases DHX9, DHX36, DDX41, RNA polymerase III, each which play important role DNA-mediated immunity.

Language: Английский

Pyroptosis: mechanisms and diseases DOI Creative Commons

Pian Yu,

Xu Zhang, Nian Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: March 29, 2021

Abstract Currently, pyroptosis has received more and attention because of its association with innate immunity disease. The research scope expanded the discovery gasdermin family. A great deal evidence shows that can affect development tumors. relationship between tumors is diverse in different tissues genetic backgrounds. In this review, we provide basic knowledge pyroptosis, explain tumors, focus on significance tumor treatment. addition, further summarize possibility as a potential treatment strategy describe side effects radiotherapy chemotherapy caused by pyroptosis. brief, double-edged sword for rational use dual effect will help us explore formation ideas patients to develop new drugs based

Language: Английский

Citations

1568
NLRP3 inflammasome in cancer and metabolic diseases DOI
Bhesh Raj Sharma, Thirumala‐Devi Kanneganti

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(5), P. 550 - 559

Published: March 11, 2021

Language: Английский

Citations

757
The role of pyroptosis in cancer: pro-cancer or pro-“host”? DOI Creative Commons
Xiaojing Xia, Xin Wang, Zhe Cheng

et al.

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(9)

Published: Sept. 9, 2019

Abstract Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, is mediated by gasdermin family, accompanied inflammatory immune responses. The relationship between cancer complex, effects vary different tissues genetic backgrounds. On one hand, can inhibit occurrence development tumors; other as a type proinflammatory death, form suitable microenvironment for tumor growth thus promote growth. In addition, induction also considered potential treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results lower expression levels DFNA5/GSDME most than normal cells, making it difficult activate cells. During malignant tumors, appropriate chemotherapeutic drugs be selected according DFNA5/GSDME, upregulated thereby increasing sensitivity reducing drug resistance. Therefore, induced may play predominant role cancer. Here, we review latest research anti- protumor its applications treatment.

Language: Английский

Citations

727
Inflammasome activation and regulation: toward a better understanding of complex mechanisms DOI Creative Commons

Danping Zheng,

Timur Liwinski, Eran Elinav

et al.

Cell Discovery, Journal Year: 2020, Volume and Issue: 6(1)

Published: June 8, 2020

Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by repertoire of endogenous exogenous stimuli, leading to enzymatic activation canonical caspase-1, noncanonical caspase-11 (or equivalent caspase-4 caspase-5 humans) or caspase-8, resulting secretion IL-1β IL-18, as well apoptotic pyroptotic cell death. Appropriate inflammasome is vital for host cope with foreign pathogens tissue damage, while aberrant cause uncontrolled responses that may contribute various diseases, including autoinflammatory disorders, cardiometabolic cancer neurodegenerative diseases. Therefore, it imperative maintain fine balance between inhibition, which requires fine-tuned regulation assembly effector function. Recently, growing body studies have been focusing on delineating structural molecular mechanisms underlying signaling. In present review, we summarize most recent advances remaining challenges understanding ordered upon sensing diverse tight regulations these processes. Furthermore, review progress translating research into therapeutic tools, aimed at modifying inflammasome-regulated human

Language: Английский

Citations

715
Caspases in Cell Death, Inflammation, and Pyroptosis DOI Open Access
Sannula Kesavardhana, R. K. Subbarao Malireddi, Thirumala‐Devi Kanneganti

et al.

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 567 - 595

Published: Feb. 4, 2020

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases activated via macromolecular signaling complexes bring inactive procaspases together promote their proximity-induced autoactivation proteolytic processing. Activation ultimately results execution death, the nature this is determined by specific involved. Pioneering new research has unraveled distinct cross talk regulation inflammation, innate immune responses. In-depth understanding these mechanisms essential to foster development precise therapeutic targets treat autoinflammatory disorders, infectious diseases, cancer. This review focuses on governing caspase activation with special emphasis recent progress caspase-driven gasdermin D-induced pyroptosis.

Language: Английский

Citations

705
Long noncoding RNAs in cancer metastasis DOI
Siyuan Liu, Ha X. Dang, Daniel A. Lim

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(7), P. 446 - 460

Published: May 5, 2021

Language: Английский

Citations

503
ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis) DOI Creative Commons
R. K. Subbarao Malireddi, Sannula Kesavardhana, Thirumala‐Devi Kanneganti

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2019, Volume and Issue: 9

Published: Nov. 26, 2019

Cell death is central to development, organismal homeostasis, and immune responses. The cell field has experienced tremendous progress by delineating the molecular programs specific each of apoptotic inflammatory pathways. Moreover, discovery inflammasomes pyroptosis necroptosis pathway regulators have provided genetic basis for programmed Earlier research highlighted unique regulation these pathways, but emerging studies discovered co-regulation crosstalk between seemingly different complexes. in this area led an idea that master play roles orchestrating multiple Here, we provide a brief review regulators, innate sensor ZBP1 essential survival kinase TAK1, vital RIPK1/RIPK3-FADD-caspase-8 complex assembly its versatility executing Pyroptosis, Apoptosis, Necroptosis, which dubbed here as PAN-optosis. Furthermore, discuss implications therapeutic potential targeting health disease.ZBP1 TAK1 regulate

Language: Английский

Citations

433
Myeloid immunosuppression and immune checkpoints in the tumor microenvironment DOI Open Access
Kyohei Nakamura, Mark J. Smyth

Cellular and Molecular Immunology, Journal Year: 2019, Volume and Issue: 17(1), P. 1 - 12

Published: Oct. 14, 2019

Language: Английский

Citations

400
Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasome Activation, and Host Defense DOI Creative Commons
Min Zheng, Rajendra Karki, Peter Vogel

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(3), P. 674 - 687.e13

Published: April 1, 2020

Language: Английский

Citations

385
A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer DOI Creative Commons

Ying Ye,

Qinjin Dai, Hongbo Qi

et al.

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: April 7, 2021

Abstract Ovarian cancer (OC) is a highly malignant gynaecological tumour that has very poor prognosis. Pyroptosis been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression pyroptosis-related genes OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators were differentially expressed between normal ovarian tissues. Based on these (DEGs), all cases could divided into two subtypes. The prognostic value each gene for survival was evaluated construct multigene signature using Cancer Genome Atlas (TCGA) cohort. By applying least absolute shrinkage selection operator (LASSO) Cox regression method, 7-gene built classified patients TCGA cohort low- or high-risk group. low-risk group showed significantly higher possibilities than those ( P < 0.001). Utilizing median risk score from cohort, Gene Expression Omnibus (GEO) subgroups, had increased overall (OS) time = 0.014). Combined clinical characteristics, found independent factor predicting OS patients. ontology (GO) Kyoto Encylopedia Genes Genomes (KEGG) analyses indicated immune-related enriched immune status decreased conclusion, play important roles immunity can used predict OCs.

Language: Английский

Citations

353