scholarly journals NLRP3 Inflammasome in Cardiovascular Disease: David`s Stone against Goliath?

2021 ◽  
Vol 31 (3) ◽  
pp. 517-527
Author(s):  
Serban BALANESCU ◽  
◽  
Elena BARBU ◽  
Camelia GEORGESCU ◽  
Andreea Catarina POPESCU ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Protective Role ◽  
Large Protein ◽  
Endogenous Factors ◽  
Natural Defense ◽  
Large Protein Complex ◽  
Intracellular Expression ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Pathologic Processes

Inflammation is involved in initiation, development and complications of the vast majority of non-communicable diseases. Recent research demonstrated that infl ammation is involved in pathogenesis of all major cardiovascular diseases. Different endogenous factors (LDL, nucleic acid strands, uric acid – collectively called „Damage Associated Molecular Patterns – DAMPs”) activate dedicated receptors („Pattern Recognition Receptors – PRR”) on monocytes, macrophages or dendritic cells responsible for the innate immunologic response. They have a major role in natural defense mechanisms against different pathogens and in normal conditions have a protective role. Among PRRs „NOD-like, leucin rich, pyrin containing (NLRP)” receptors are a 14-member family located in the cytoplasm. One of these is the NLRP3 resulting from nuclear transcription under the infl uence of NF-kB, a second messenger from membrane PRRs to the nucleus. Mostly the same factors responsible for NLRP3 intracellular expression stimulate its oligomerization resulting in a large protein complex, the NLRP3 infl ammasome. This activates caspase-1 responsible for IL-1b and IL-18 production and initiates an inflammatory reaction leading to various pathologic processes, such as atherosclerosis, hypertension, diabetes and heart failure. This is the current story as we know it of the NLRP3 infl ammasome, a small intracellular component that when inappropriately activated may does more harm than good.

Taking Advantage of Plant Defense Mechanisms to Promote Human Health. The Plant Immune System. First of Two Parts

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
Immune Response ◽  
Plant Defense ◽  
Defense Mechanisms ◽  
Systemic Acquired Resistance ◽  
Plant Immunity ◽  
Acquired Resistance ◽  
Early Response ◽  
Protein Receptors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Background: Despite the evidence that plants do not possess sessile cells, they are able to mount a vigorous immune response against invaders or under stressful conditions. Mechanisms of action: Plants are endowed with pattern recognition receptors (PPRs) which perceive damage-associated molecular patterns and microbe-associated molecular patterns or pathogen-associated molecular patterns (PAMPs), respectively. PPR activation leads to either the initiation of PAMP-triggered immunity (PTI) (early response) or the effectortriggered immunity (ETI). Both PTI and ETI contribute to plant systemic acquired resistance as also an expression of immunological memory or trained immunity. Plant immune receptors: PTI is initiated by activation of both receptor-like kinases and receptor-like proteins, while ETI depends on nucleotide-binding leucine-rich-repeat protein receptors for microbe recognition. Peptides involved in plant defenses: Plant chloroplasts contribute to both PTI and ETI through production of peptides which act as hormones or phytocytokines. Salicylic acid, jasmonic acid and ethylene are the major compounds involved in plant defense. Specific aims: The interaction between plant receptors and/or their products and bacterial components will be discussed. Also emphasis will be placed on plant microbiome for its contribution to plant immune response. Finally, the mutual interplay between insects and plants will also be illustrated. Conclusion: A better knowledge on plant immunity may pave the way for the exploitation of plant derivatives in the field of agriculture and medicine, as well.

scholarly journals Influence of cell wall polymers and their modifying enzymes during plant–aphid interactions

2019 ◽  
Vol 71 (13) ◽  
pp. 3854-3864 ◽  
Author(s):  
Christian Silva-Sanzana ◽  
José M Estevez ◽  
Francisca Blanco-Herrera
Keyword(s):  
Cell Wall ◽  
Defense Mechanisms ◽  
Plant Pathogens ◽  
Polymer Network ◽  
Aphid Infestation ◽  
Cell Wall Polymers ◽  
Colony Performance ◽  
Plant Pathosystems ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Aphids are a major issue for commercial crops. These pests drain phloem nutrients and transmit ~50% of the known insect-borne viral diseases. During aphid feeding, trophic structures called stylets advance toward the phloem intercellularly, disrupting cell wall polymers. It is thought that cell wall-modifying enzymes (CWMEs) present in aphid saliva facilitate stylet penetration through this intercellular polymer network. Additionally, different studies have demonstrated that host settling preference, feeding behavior, and colony performance of aphids are influenced by modulating the CWME expression levels in host plants. CWMEs have been described as critical defensive elements for plants, but also as a key virulence factor for plant pathogens. However, whether CWMEs are elements of the plant defense mechanisms or the aphid infestation process remains unclear. Therefore, in order to better consider the function of CWMEs and cell wall-derived damage-associated molecular patterns (DAMPs) during plant–aphid interactions, the present review integrates different hypotheses, perspectives, and experimental evidence in the field of plant–aphid interactions and discusses similarities to other well-characterized models such as the fungi–plant pathosystems from the host and the attacker perspectives.

scholarly journals Inflammasomes in Teleosts: Structures and Mechanisms That Induce Pyroptosis during Bacterial Infection

2021 ◽  
Vol 22 (9) ◽  
pp. 4389
Author(s):  
Natsuki Morimoto ◽  
Tomoya Kono ◽  
Masahiro Sakai ◽  
Jun-ichi Hikima
Keyword(s):  
Inflammatory Responses ◽  
Current Knowledge ◽  
Adaptor Protein ◽  
Protective Role ◽  
Inflammasome Activation ◽  
Multiple Protein ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Oligomerization Domain

Pattern recognition receptors (PRRs) play a crucial role in inducing inflammatory responses; they recognize pathogen-associated molecular patterns, damage-associated molecular patterns, and environmental factors. Nucleotide-binding oligomerization domain-leucine-rich repeat-containing receptors (NLRs) are part of the PRR family; they form a large multiple-protein complex called the inflammasome in the cytosol. In mammals, the inflammasome consists of an NLR, used as a sensor molecule, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) as an adaptor protein, and pro-caspase1 (Casp1). Inflammasome activation induces Casp1 activation, promoting the maturation of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, and the induction of inflammatory cell death called pyroptosis via gasdermin D cleavage in mammals. Inflammasome activation and pyroptosis in mammals play important roles in protecting the host from pathogen infection. Recently, numerous inflammasome-related genes in teleosts have been identified, and their conservation and/or differentiation between their expression in mammals and teleosts have also been elucidated. In this review, we summarize the current knowledge of the molecular structure and machinery of the inflammasomes and the ASC-spec to induce pyroptosis; moreover, we explore the protective role of the inflammasome against pathogenic infection in teleosts.

scholarly journals Plant Virus Interaction: Layers of Plant Antiviral Immunity

2019 ◽  
pp. 89-94
Author(s):  
Pedro Filho Noronha Souza
Keyword(s):  
Plant Virus ◽  
Defense Mechanisms ◽  
Second Line ◽  
Basal Resistance ◽  
Double Stranded Rna ◽  
Effector Triggered Immunity ◽  
Virus Interaction ◽  
Two Phases ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Plant defense mechanisms are divided into two phases; (1) the Pathogen-Triggered Immunity (PTI), which is basal resistance and; (2) Effector-Triggered Immunity (ETI) or induced resistance, the second line of defense of plants [1,2]. The PTI response is rapidly active by plants after recognizing pathogens effectors, which could be MAMPS or PAMPs (Microbe/pathogen-associated molecular patterns, e.g., bacterial flagellin), DAMPs (Damage-associated molecular patterns, e.g., fungal haustorium), and VAMPs (Viral-associated molecular patterns, e.g., double-stranded RNA of viruses). The recognition of pathogens effectors is performed by Pattern Recognition Receptors (PRR) [3-6].

scholarly journals Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κB/Autophagy Signaling

2020 ◽  
Author(s):  
Soad Z. El-Emam
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Human Lung ◽  
Therapeutic Option ◽  
Protective Role ◽  
Lung Toxicity ◽  
Human Lung Cells ◽  
Normal Human ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet. This study aims to investigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells, WI-38 cell line, without suppressing its efficacy. Cells were pretreated with SES and/or CYL for 24 h, then cell viability was estimated by MTS and trypan blue assays. The mode of cell death was determined by AO/EB staining. Additionally, caspase-3 level, oxidative stress, and inflammatory markers were evaluated by colorimetric and ELISA techniques. qRT-PCR was performed to evaluate RAGE, NF-κB, and Beclin-1 mRNA-expression. CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling, which were all attenuated after pretreatment with SES. Thus, we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling, which is a natural safe therapeutic option against CYL toxicities. Graphic Abstract

scholarly journals In Silico Phylogenetic and Structural Analysis of Plant Damps

2018 ◽  
Author(s):  
Athanasia pavlopoulou ◽  
Ezgi Karaca ◽  
Alma Balestrazzi ◽  
Alexandros Georgakilas
Keyword(s):  
In Silico ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Conservation Status ◽  
Biological Molecules ◽  
Downstream Signaling ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Diverse Plant Species ◽  
Damage Associated Molecular Patterns

In plants and animals, endogenous biological molecules, termed damage-associated molecular patterns (DAMPs) or alarmins, are released by damaged, stressed or dying cells following abiotic stress such as radiation and drought stress. In turn, a cascade of downstream signaling events is initiated leading to the up-regulation of defense-related genes. In the present study, in an effort to investigate the conservation status of the molecular mechanisms implicated in the danger signaling, thorough in silico phylogenetic and structural analyses of the effector biomolecules were performed in taxonomically diverse plant species. On the basis of our results, the defense mechanisms appear to be largely conserved within the plant kingdom. Of note is our finding that the sequence and/or function of several components of these mechanisms were found to be conserved in animals, as well.

scholarly journals Holding the Inflammatory System in Check: TLRs and Their Targeted Therapy in Asthma

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiyong Dong ◽  
Lingxin Xiong ◽  
Weijie Zhang ◽  
Peter G. Gibson ◽  
Ting Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Biological Response ◽  
Protective Role ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Pathogenic Factors ◽  
Genetic And Environmental Factors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Inflammatory System

Inflammation is a complex biological response to detrimental stimuli and can be a double-edged sword. Inflammation plays a protective role in removing pathogenic factors, but dysregulated inflammation is associated with several major fatal diseases such as asthma, cancer, and cardiovascular diseases. Asthma is a complex heterogenous disease caused by genetic and environmental factors. TLRs are the primary proteins associated with the innate and adaptive immune responses to these fatal factors and play an important role in recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which initiates the downstream immune response. Due to the complex TLRs cascade and nowadays unsuccessful control in asthma, new studies are focused on TLRs and other potential targets in TLR cascade to minimize airway inflammation.

scholarly journals Release mechanisms of major DAMPs

APOPTOSIS ◽  
2021 ◽  
Vol 26 (3-4) ◽  
pp. 152-162
Author(s):  
Atsushi Murao ◽  
Monowar Aziz ◽  
Haichao Wang ◽  
Max Brenner ◽  
Ping Wang
Keyword(s):  
Rna Binding ◽  
High Mobility ◽  
Live Cells ◽  
Membrane Channel ◽  
Membrane Rupture ◽  
Underlying Mechanisms ◽  
Shock Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Secretory Lysosomes

AbstractDamage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

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