Mechanisms by which fatty acids regulate leucocyte function

2007 ◽  
Vol 113 (2) ◽  
pp. 65-77 ◽  
Author(s):  
Thais Martins de Lima ◽  
Renata Gorjão ◽  
Elaine Hatanaka ◽  
Maria Fernanda Cury-Boaventura ◽  
Erica Paula Portioli Silva ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Substantial Improvement ◽  
Lipid Mediators ◽  
Control Of Gene Expression ◽  
Intracellular Signalling Pathways ◽  
Activation Of Transcription ◽  
Associated Proteins

Fatty acids (FAs) have been shown to alter leucocyte function and thus to modulate inflammatory and immune responses. In this review, the effects of FAs on several aspects of lymphocyte, neutrophil and macrophage function are discussed. The mechanisms by which FAs modulate the production of lipid mediators, activity of intracellular signalling pathways, activity of lipid-raft-associated proteins, binding to TLRs (Toll-like receptors), control of gene expression, activation of transcription factors, induction of cell death and production of reactive oxygen and nitrogen species are described in this review. The rationale for the use of specific FAs to treat patients with impaired immune function is explained. Substantial improvement in the therapeutic usage of FAs or FA derivatives may be possible based on an improvement in the understanding of the precise molecular mechanisms of action with respect to the different leucocyte types and outcome with respect to the inflammatory responses.

scholarly journals n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions

2013 ◽  
Vol 72 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mechanisms Of Action ◽  
Lipid Mediators ◽  
Functional Responses ◽  
New Family ◽  
Epa And Dha ◽  
Novel Interactions

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

scholarly journals mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 402
Author(s):  
Sumit Mukherjee ◽  
Bodhisattwa Banerjee ◽  
David Karasik ◽  
Milana Frenkel-Morgenstern
Keyword(s):  
Network Analysis ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Cytokine Signaling ◽  
Respiratory Disorder ◽  
Cytokine Storm ◽  
Global Public Health ◽  
Aberrant Expression

The recently emerged SARS-CoV-2 virus is responsible for the ongoing COVID-19 pandemic that has rapidly developed into a global public health threat. Patients severely affected with COVID-19 present distinct clinical features, including acute respiratory disorder, neutrophilia, cytokine storm, and sepsis. In addition, multiple pro-inflammatory cytokines are found in the plasma of such patients. Transcriptome sequencing of different specimens obtained from patients suffering from severe episodes of COVID-19 shows dynamics in terms of their immune responses. However, those host factors required for SARS-CoV-2 propagation and the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive. In the present study, we analyzed the mRNA-long non-coding RNA (lncRNA) co-expression network derived from publicly available SARS-CoV-2-infected transcriptome data of human lung epithelial cell lines and bronchoalveolar lavage fluid (BALF) from COVID-19 patients. Through co-expression network analysis, we identified four differentially expressed lncRNAs strongly correlated with genes involved in various immune-related pathways crucial for cytokine signaling. Our findings suggest that the aberrant expression of these four lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection of the lungs. Thus, the present study uncovers molecular interactions behind the cytokine storm activation potentially responsible for hyper-inflammatory responses in critical COVID-19 patients.

Abstract 702: Walnut Treatment Reduces Specific Pro-inflammatory Lipid Mediators While Increasing Anti-inflammatory Ones: An RCT subanalysis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Gregory C Shearer ◽  
John W Newman ◽  
Roberta R Holt ◽  
Carl L Keen ◽  
Robert M Hackman
Keyword(s):  
Fatty Acids ◽  
Heart Disease ◽  
Fatty Acid ◽  
Inflammatory Responses ◽  
Plasma Lipid ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Plasma Fatty Acid ◽  
Anti Inflammatory ◽  
Active Dose

Background: Lipid mediators are transported in plasma, inducing pro- or anti-inflammatory responses in target tissues. Each daily nut serving is associated with 30% reduction in risk for cardiovascular or ischemic heart disease. Walnuts are an abundant source of bioactives and of precursors to lipid mediator synthesis: linoleic (LA) and alpha-linolenic (aLA) acids. How walnuts impact plasma lipid mediators either by providing more substrate or more specifically via other bioactives is unknown. Objective: Measure lipid mediators from the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome p450 (CYP), and auto-oxidative pathways in plasma from subjects consuming large and small amounts of walnuts. Design: 40 hypercholesterolemic, postmenopausal females were randomly assigned to a null dose (5g/d) or an active dose (40 g/d) of walnuts for 4 weeks. In a subset of 20 subjects, plasma lipid mediators synthesized from LA, aLA and other polyunsaturated fatty acids were measured by LC/MS/MS at baseline and final visits. Differences are reported as mean, 95% CIs. Results: Walnuts did not alter the compositional abundance of any plasma fatty acid except aLA, which was increased 1.46 fold [1.83, 1.16], p=0.003. Walnuts did modify plasma lipid mediator composition: specific pro-inflammatory COX metabolites, PGD2 and PGJ2/delta-12-PGJ2 were reduced by -72% [-43, -86] and -55% [-9, -77] respectively. LOX metabolites were almost uniformly depressed: the immediate mid-chain alcohols of LA (HODEs), dgLA (HETrEs), AA (HETEs), EPA (HEPEs) and DHA (HDoHEs) were reduced by 50-75% (p≤0.007), but aLA (HOTEs) were not. Metabolites of 5-LOX further downstream were also reduced: 5-KETE by 79% [-91, -50], and 6-trans-LTB4 by -89% [-76, -95]. Conversely, anti-inflammatory CYP-epoxides of LA (EpOME) and aLA (EpODE) were increased 82% [3, 223] and 143% [37, 331]. Epoxides of eicosanoids and docosanoids were unchanged (AA EpETrEs or EETs; EPA EpETEs; DHA EpDPEs). Conclusion: Walnut feeding reduces plasma pro-inflammatory COX and LOX metabolites while increasing some anti-inflammatory CYP metabolites. The effect occurs largely without changes in fatty acids, suggesting a molecular mechanism independent of simple changes in precursor abundance.

scholarly journals Rag GTPases mediate amino acid–dependent recruitment of TFEB and MITF to lysosomes

2013 ◽  
Vol 200 (4) ◽  
pp. 475-491 ◽  
Author(s):  
Jose A. Martina ◽  
Rosa Puertollano
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Energy Levels ◽  
Control Of Gene Expression ◽  
Rag Gtpases ◽  
Activation Of Transcription ◽  
Switch Regions ◽  
Transcription Factor Eb ◽  
Cell Growth And Proliferation

The mTORC1 complex supports cell growth and proliferation in response to energy levels, growth factors, and nutrients. The Rag guanosine triphosphatases (GTPases) activate mTORC1 in response to amino acids by promoting its redistribution to lysosomes. In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression. Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB. The interaction of TFEB with Rags required the first 30 residues of TFEB and the switch regions of the Rags G domain. Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranes. Finally, Rag GTPases bound and regulated activation of microphthalmia-associated transcription factor, suggesting a broader role for Rags in the control of gene expression. Our work provides new insight into the molecular mechanisms that link nutrient availability and TFEB localization and activation.

scholarly journals KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease

Open Biology ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 200105 ◽  
Author(s):  
Sharadha Dayalan Naidu ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Related Factor ◽  
Redox Imbalance ◽  
Persistent Inflammation ◽  
Activation Of Transcription

Redox imbalance and persistent inflammation are the underlying causes of most chronic diseases. Mammalian cells have evolved elaborate mechanisms for restoring redox homeostasis and resolving acute inflammatory responses. One prominent mechanism is that of inducing the expression of antioxidant, anti-inflammatory and other cytoprotective proteins, while also suppressing the production of pro-inflammatory mediators, through the activation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2). At homeostatic conditions, NRF2 is a short-lived protein, which avidly binds to Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 functions as (i) a substrate adaptor for a Cullin 3 (CUL3)-based E3 ubiquitin ligase that targets NRF2 for ubiquitination and proteasomal degradation, and (ii) a cysteine-based sensor for a myriad of physiological and pharmacological NRF2 activators. Here, we review the intricate molecular mechanisms by which KEAP1 senses electrophiles and oxidants. Chemical modification of specific cysteine sensors of KEAP1 results in loss of NRF2-repressor function and alterations in the expression of NRF2-target genes that encode large networks of diverse proteins, which collectively restore redox balance and resolve inflammation, thus ensuring a comprehensive cytoprotection. We focus on the cyclic cyanoenones, the most potent NRF2 activators, some of which are currently in clinical trials for various pathologies characterized by redox imbalance and inflammation.

Molecular mechanisms

2017 ◽  
Author(s):  
Claudia Monaco ◽  
Giuseppina Caligiuri
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipid Mediators ◽  
Signalling Pathways ◽  
Immunological Responses ◽  
Intracellular Signalling Pathways ◽  
Cell Surface Interactions ◽  
Atherosclerosis Development ◽  
Inflammatory Signalling

The development of the atherosclerotic plaque relies on specific cognate interactions between ligands and receptors with the ability to regulate cell recruitment, inflammatory signalling, and the production of powerful inflammatory and bioactive lipid mediators. This chapter describes how signalling is engaged by cell-cell surface interactions when the endothelium interacts with platelets and leukocytes enhancing leukocyte recruitment during atherogenesis. It also exemplifies intracellular signalling pathways induced by the activation of innate immune receptors, the most potent activators of inflammation in physiology and disease. Differences are highlighted in innate signalling pathways in metabolic diseases such as atherosclerosis compared to canonical immunological responses. Finally, the key lipid mediators whose production can affect endothelial function, inflammation, and atherosclerosis development are summarized. This Chapter will take you through these fundamental steps in the development of the atherosclerotic plaque by summarizing very recent knowledge in the field and highlighting recent or ongoing clinical trials that may enrich our ability to target cardiovascular disease in the future.

Phytochemical profiles and their anti-inflammatory responses against influenza from Traditional Chinese medicine or herbs

2020 ◽  
Vol 20 ◽  
Author(s):  
Huihui Ti
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Influenza Viruses ◽  
Pharmacological Mechanism ◽  
Influenza Activity ◽  
Underlying Mechanisms ◽  
Phytochemical Profiles

: Traditional Chinese medicine (TCM) or herbs are widely used in the prevention and treatment of viral infectious diseases. However, the underlying mechanisms of TCMs remain largely obscure due to complicated material basis and multi-target therapeutics. TCMs have been reported to display anti-influenza activity associated with immunoregulatory mechanisms by enhancing host anti-influenza immune responses. Previous studies have helped us understanding the direct harm caused by the virus itself. In this review, we have tried to summarize recent progress in TCM-based anti-influenza research the indirect harmful immune responses caused by influenza viruses. In particular, the phytochemicals from TCMs responsible for molecular mechanisms of action belonging to different classes, including phenolic compounds, flavonoids, alkaloids and polysaccharides, have been identified and demonstrated. In addition, this review focuses on the pharmacological mechanism, e.g., inflammatory responses and the interferon (IFN) signaling pathway, which can provide a theoretical basis and approaches for TCM based anti-influenza treatment.

ADDRESSING THE ISSUE OF СOVID-19, SARS-COV-2 VIRUS AND THE DISEASE

2020 ◽  
Vol 99 (6) ◽  
pp. 15-31
Author(s):  
A.A. Korenkova ◽  
◽  
E.M. Mayorova ◽  
V.V. Bahmetjev ◽  
M.V. Tretyak ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Herd Immunity ◽  
Significant Problem ◽  
Prevention Measures ◽  
Optimal Therapy ◽  
The World ◽  
Public Health Challenge ◽  
Coronavirus Infection

The new coronavirus infection has posed a major public health challenge around the world, but new data on the disease raises more questions than answers. The lack of optimal therapy is a significant problem. The article examines the molecular mechanisms of SARS-CoV-2 infection and the pathogenesis of COVID-19, special attention is paid to features of pathological processes and immune responses in children. COVID-19 leads to a wide diversity of negative outcomes, many of which can persist for at least months. Many of the consequences have yet to be identified. SARS-CoV-2 may provoke autoimmune reactions. Reinfection, herd immunity, vaccines and other prevention measures are also discussed in this review.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

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