scholarly journals The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation

2016 ◽  
Vol 213 (6) ◽  
pp. 617-629 ◽  
Author(s):  
Deepika Sharma ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Cell Biology ◽  
Inflammasome Activation ◽  
Biological Processes ◽  
Biological Functions ◽  
Cellular Processes ◽  
The Past ◽  
Functional Output ◽  
Made In

Over the past decade, numerous advances have been made in the role and regulation of inflammasomes during pathogenic and sterile insults. An inflammasome complex comprises a sensor, an adaptor, and a zymogen procaspase-1. The functional output of inflammasome activation includes secretion of cytokines, IL-1β and IL-18, and induction of an inflammatory form of cell death called pyroptosis. Recent studies have highlighted the intersection of this inflammatory response with fundamental cellular processes. Novel modulators and functions of inflammasome activation conventionally associated with the maintenance of homeostatic biological functions have been uncovered. In this review, we discuss the biological processes involved in the activation and regulation of the inflammasome.

scholarly journals Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation

2021 ◽  
Vol 22 (7) ◽  
pp. 3318
Author(s):  
Jun-Hyuk Han ◽  
Jooho Park ◽  
Tae-Bong Kang ◽  
Kwang-Ho Lee
Keyword(s):  
Cell Death ◽  
Inflammatory Responses ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Biological Processes ◽  
The Past ◽  
Cytokine Induction ◽  
Inflammatory Processes ◽  
Regulatory Functions ◽  
Anti Inflammation

Caspase-8 has been classified as an apoptotic caspase, and its initial definition was an initiator of extrinsic cell death. During the past decade, the concept of caspase-8 functioning has been changed by findings of its additional roles in diverse biological processes. Although caspase-8 was not originally thought to be involved in the inflammation process, many recent works have determined that caspase-8 plays an important role in the regulatory functions of inflammatory processes. In this review, we describe the recent advances in knowledge regarding the manner in which caspase-8 modulates the inflammatory responses concerning inflammasome activation, cell death, and cytokine induction.

Comparison and Analysis of Computational Methods for Identifying N6 - methyladenosine Sites in Saccharomyces Cerevisiae

2020 ◽  
Vol 26 ◽  
Author(s):  
Pengmian Feng ◽  
Lijing Feng ◽  
Chaohui Tang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Computational Methods ◽  
Computational Analysis ◽  
Computational Prediction ◽  
Experimental Methods ◽  
Biological Processes ◽  
Biological Functions ◽  
Precise Location ◽  
Future Directions ◽  
The Past

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.

scholarly journals SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes

2020 ◽  
Author(s):  
André C. Ferreira ◽  
Vinicius Cardoso Soares ◽  
Isaclaudia G. de Azevedo-Quintanilha ◽  
Suelen da Silva Gomes Dias ◽  
Natalia Fintelman-Rodrigues ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Inflammatory Cell ◽  
Viral Infections ◽  
Relevant Information ◽  
Inflammasome Activation ◽  
Human Monocytes ◽  
Hla Dr

AbstractInfection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocyte death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and from patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe mechanisms by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb to control severe 2019 coronavirus disease (COVID-19).Author summarySince its emergence in China in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide. Currently, the number of individuals infected with SARS-CoV-2 and in need of antiviral, anti-inflammatory, anticoagulant and more invasive treatments has overwhelmed the health systems worldwide. In our study, we found that SARS-CoV-2 is capable of inducing inflammatory cell death in human monocytes, one of the main cell types responsible for anti-SARS-CoV-2 immune response. As a consequence of this intracellular inflammatory mechanism (inflammasome engagement), an exacerbated production of inflammatory mediators occurs. The infection also decreases the expression of HLA-DR in monocytes, a molecule related to the orchestration of the immune response in case of viral infections. We also demonstrated that the HIV-1 protease inhibitor, atazanavir (ATV), prevented the uncontrolled inflammatory response, cell death and reduction in HLA-DR expression in SARS-CoV-2-infected monocytes. Our study provides relevant information on the effects of SARS-CoV-2 infection on human monocytes, as well as on the effect of ATV in preventing these pathological effects on the host.

scholarly journals Bacterial Vivisection: How Fluorescence-Based Imaging Techniques Shed a Light on the Inner Workings of Bacteria

2020 ◽  
Vol 84 (4) ◽  
Author(s):  
Alexander Cambré ◽  
Abram Aertsen
Keyword(s):  
Real Time ◽  
Bacterial Cell ◽  
Cell Biology ◽  
Imaging Techniques ◽  
Time Lapse ◽  
Bacterial Cells ◽  
The Past ◽  
Current State ◽  
Architectural Features ◽  
Made In

SUMMARY The rise in fluorescence-based imaging techniques over the past 3 decades has improved the ability of researchers to scrutinize live cell biology at increased spatial and temporal resolution. In microbiology, these real-time vivisections structurally changed the view on the bacterial cell away from the “watery bag of enzymes” paradigm toward the perspective that these organisms are as complex as their eukaryotic counterparts. Capitalizing on the enormous potential of (time-lapse) fluorescence microscopy and the ever-extending pallet of corresponding probes, initial breakthroughs were made in unraveling the localization of proteins and monitoring real-time gene expression. However, later it became clear that the potential of this technique extends much further, paving the way for a focus-shift from observing single events within bacterial cells or populations to obtaining a more global picture at the intra- and intercellular level. In this review, we outline the current state of the art in fluorescence-based vivisection of bacteria and provide an overview of important case studies to exemplify how to use or combine different strategies to gain detailed information on the cell’s physiology. The manuscript therefore consists of two separate (but interconnected) parts that can be read and consulted individually. The first part focuses on the fluorescent probe pallet and provides a perspective on modern methodologies for microscopy using these tools. The second section of the review takes the reader on a tour through the bacterial cell from cytoplasm to outer shell, describing strategies and methods to highlight architectural features and overall dynamics within cells.

scholarly journals A light way for nuclear cell biologists

2020 ◽  
Author(s):  
Giada Forlani ◽  
Barbara Di Ventura
Keyword(s):  
Actin Filaments ◽  
Genetic Information ◽  
Cell Biology ◽  
State Of The Art ◽  
Biological Processes ◽  
Stimulus Light ◽  
Cellular Processes ◽  
Nuclear Cell ◽  
Nuclear Expansion ◽  
Internal Architecture

Abstract The nucleus is a very complex organelle present in eukaryotic cells. Having the crucial task to safeguard, organize and manage the genetic information, it must tightly control its molecular constituents, its shape and its internal architecture at any given time. Despite our vast knowledge of nuclear cell biology, much is yet to be unraveled. For instance, only recently we came to appreciate the existence of a dynamic nuclear cytoskeleton made of actin filaments that regulates processes such as gene expression, DNA repair and nuclear expansion. This suggests further exciting discoveries ahead of us. Modern cell biologists embrace a new methodology relying on precise perturbations of cellular processes that require a reversible, highly spatially-confinable, rapid, inexpensive and tunable external stimulus: light. In this review, we discuss how optogenetics, the state-of-the-art technology that uses genetically-encoded light-sensitive proteins to steer biological processes, can be adopted to specifically investigate nuclear cell biology.

scholarly journals NLRP3 deletion protects from hyperoxia-induced acute lung injury

2013 ◽  
Vol 305 (2) ◽  
pp. C182-C189 ◽  
Author(s):  
Jutaro Fukumoto ◽  
Itsuko Fukumoto ◽  
Prasanna Tamarapu Parthasarathy ◽  
Ruan Cox ◽  
Bao Huynh ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Epithelial Cell ◽  
Inflammasome Activation ◽  
Nlrp3 Gene ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3−/− mice were exposed to 100% O2 for 48–72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3−/− mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNFα, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3−/− mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-κB levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.

scholarly journals RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yuting Meng ◽  
Qiong Zhang ◽  
Kaihang Wang ◽  
Xujun Zhang ◽  
Rongwei Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Programmed Cell Death ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Biological Processes ◽  
Underlying Mechanisms ◽  
Microarray Analyses

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.

scholarly journals Proximity interactome of LC3B in normal growth conditions

2021 ◽  
Author(s):  
Marie Nollet ◽  
Alexander Agrotis ◽  
Fanourios Michailidis ◽  
Arran David Dokal ◽  
Vinothini Rajeeve ◽  
...  
Keyword(s):  
Cell Biology ◽  
Normal Growth ◽  
Growth Conditions ◽  
Biological Functions ◽  
Normal Medium ◽  
Outer Membranes ◽  
Cellular Processes ◽  
Proteomic Approach ◽  
And Function

LC3 (Light Chain 3) is a key player of autophagy, a major stress-responsive proteolysis pathway promoting cellular homeostasis. It coordinates the formation and maturation of autophagosomes and recruits cargo to be further degraded upon autophagosome-lysosome fusion. To orchestrate its functions, LC3 binds to multiple proteins from the autophagosomes inner and outer membranes, but the full extent of these interactions is not known. Moreover, LC3 has been increasingly reported in other cellular locations than the autophagosome, with cellular outcome not fully understood and not all related to autophagy. Furthermore, novel functions of LC3 as well as autophagy can occur in cells growing in a normal medium thus in non-stressed conditions. A better knowledge of the molecule in proximity to LC3 in normal growth conditions will improve the understanding of LC3 function in autophagy and in other cell biology function. Using an APEX2 based proteomic approach, we have detected 407 proteins in proximity to the well-characterised LC3B isoform in non-stress conditions. These include known and novel LC3B proximity proteins, associated with various cell localisation and biological functions. Sixty-nine of these proteins contain a putative LIR (LC3 Interacting Region) including 41 not reported associated to autophagy. Several APEX2 hits were validated by co-immunoprecipitation and co-immunofluorescence. This study uncovers the LC3B global interactome and reveals novel LC3B interactors, irrespective of LC3B localisation and function. This knowledge could be exploited to better understand the role of LC3B in autophagy and non-autophagy cellular processes.

scholarly journals The cell biology of aging

2015 ◽  
Vol 26 (25) ◽  
pp. 4524-4531 ◽  
Author(s):  
Race DiLoreto ◽  
Coleen T. Murphy
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Cell Biology ◽  
Biological Activities ◽  
Model Organisms ◽  
Biological Processes ◽  
Cellular Processes ◽  
Natural Result ◽  
Biology Of Aging

One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal—a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part genetically regulated. Many mutations have been discovered to extend lifespan in organisms of all complexities, from yeast to mammals. The study of metazoan model organisms, such as Caenorhabditis elegans, has been instrumental in understanding the role of genetics in the cell biology of aging. Longevity mutants across the spectrum of model organisms demonstrate that rates of aging are regulated through genetic control of cellular processes. The regulation and subsequent breakdown of cellular processes represent a programmatic decision by the cell to either continue or abandon maintenance procedures with age. Our understanding of cell biological processes involved in regulating aging have been particularly informed by longevity mutants and treatments, such as reduced insulin/IGF-1 signaling and dietary restriction, which are critical in determining the distinction between causes of and responses to aging and have revealed a set of downstream targets that participate in a range of cell biological activities. Here we briefly review some of these important cellular processes.

scholarly journals Digestive Inflammation: Role of Proteolytic Dysregulation

2021 ◽  
Vol 22 (6) ◽  
pp. 2817
Author(s):  
Vincent Mariaule ◽  
Aicha Kriaa ◽  
Souha Soussou ◽  
Soufien Rhimi ◽  
Houda Boudaya ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Inflammatory Response ◽  
Serine Proteases ◽  
Matrix Metalloproteases ◽  
Potential Contribution ◽  
Biological Processes ◽  
Bacterial Origin ◽  
Made In

Dysregulation of the proteolytic balance is often associated with diseases. Serine proteases and matrix metalloproteases are involved in a multitude of biological processes and notably in the inflammatory response. Within the framework of digestive inflammation, several studies have stressed the role of serine proteases and matrix metalloproteases (MMPs) as key actors in its pathogenesis and pointed to the unbalance between these proteases and their respective inhibitors. Substantial efforts have been made in developing new inhibitors, some of which have reached clinical trial phases, notwithstanding that unwanted side effects remain a major issue. However, studies on the proteolytic imbalance and inhibitors conception are directed toward host serine/MMPs proteases revealing a hitherto overlooked factor, the potential contribution of their bacterial counterpart. In this review, we highlight the role of proteolytic imbalance in human digestive inflammation focusing on serine proteases and MMPs and their respective inhibitors considering both host and bacterial origin.

Sign in / Sign up

Export Citation Format

Share Document