scholarly journals Crosstalk between Peroxisome Proliferator-Activated Receptors andToll-Like Receptors: A Systematic Review

2019 ◽  
Vol 9 (1) ◽  
pp. 12-21 ◽  
Author(s):  
Nasim Dana ◽  
Golnaz Vaseghi ◽  
Shaghayegh Haghjooy-Javanmard
Keyword(s):  
Systematic Review ◽  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Peroxisome Proliferator ◽  
Therapeutic Approaches ◽  
Disease Treatment ◽  
Peroxisome Proliferator Activated Receptors

As one of the four major families of pattern recognition receptors (PRRs), toll like receptors (TLRs)are crucial and important components of the innate immune system. Peroxisome proliferatoractivatedreceptors (PPARs) with three isoforms are transcription factors classified as a subfamilyof nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation,development, metabolism, and tumorigenesis. It is well established that PPARs agonists displayanti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, akey regulator of immune and inflammatory responses, in a sense that TLRs signaling pathwaysare mainly toward activation of NF-κB. Through a systematic review of previous studies, weaimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to findalternative therapeutic approaches for inflammatory diseases. Among the available scientificdatabase, 31 articles were selected for this review. A comprehensive review of this databaseconfirms the presence of a cross-talk between PPARs and TLRs, indicating that not onlyPPARs stimulation may affect the expression level of TLRs via several mechanisms leading tomodulating TLRs activities, but also TLRs have the potential to moderate the expression of PPARs.We, therefore, conclude that, as a key regulator of the innate immune system, the interactionbetween PPARs and TLRs is a potential therapeutic target in disease treatment.

The innate immune DNA sensor cGAS: A membrane, cytosolic, or nuclear protein?

2019 ◽  
Vol 12 (581) ◽  
pp. eaax3521 ◽  
Author(s):  
Nelson O. Gekara ◽  
Hui Jiang
Keyword(s):  
Immune System ◽  
Subcellular Localization ◽  
Innate Immune System ◽  
Nuclear Protein ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Dna Sensor ◽  
Terminal Domain

Cyclic cGMP-AMP synthase (cGAS) alerts the innate immune system to the presence of foreign or damaged self-DNA inside the cell and is critical for the outcome of infections, inflammatory diseases, and cancer. Two studies now demonstrate that cGAS activation is regulated by differential subcellular localization through its non-enzymatic, N-terminal domain.

scholarly journals Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans

2018 ◽  
Vol 104 (4) ◽  
pp. 1187-1199 ◽  
Author(s):  
Ahmed Iqbal ◽  
Lynne R Prince ◽  
Peter Novodvorsky ◽  
Alan Bernjak ◽  
Mark R Thomas ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Immune System ◽  
Innate Immune System ◽  
Low Dose ◽  
Inflammatory Responses ◽  
Platelet Reactivity ◽  
Innate Immune ◽  
Endotoxin Challenge ◽  
Intermediate Monocytes

Abstract Context Hypoglycemia is emerging as a risk for cardiovascular events in diabetes. We hypothesized that hypoglycemia activates the innate immune system, which is known to increase cardiovascular risk. Objective To determine whether hypoglycemia modifies subsequent innate immune system responses. Design and Setting Single-blinded, prospective study of three independent parallel groups. Participants and Interventions Twenty-four healthy participants underwent either a hyperinsulinemic-hypoglycemic (2.5 mmol/L), euglycemic (6.0 mmol/L), or sham-saline clamp (n = 8 for each group). After 48 hours, all participants received low-dose (0.3 ng/kg) intravenous endotoxin. Main Outcome Measures We studied in-vivo monocyte mobilization and monocyte-platelet interactions. Results Hypoglycemia increased total leukocytes (9.98 ± 1.14 × 109/L vs euglycemia 4.38 ± 0.53 × 109/L, P < 0.001; vs sham-saline 4.76 ± 0.36 × 109/L, P < 0.001) (mean ± SEM), mobilized proinflammatory intermediate monocytes (42.20 ± 7.52/μL vs euglycemia 20.66 ± 3.43/μL, P < 0.01; vs sham-saline 26.20 ± 3.86/μL, P < 0.05), and nonclassic monocytes (36.16 ± 4.66/μL vs euglycemia 12.72 ± 2.42/μL, P < 0.001; vs sham-saline 19.05 ± 3.81/μL, P < 0.001). Following hypoglycemia vs euglycemia, platelet aggregation to agonist (area under the curve) increased (73.87 ± 7.30 vs 52.50 ± 4.04, P < 0.05) and formation of monocyte-platelet aggregates increased (96.05 ± 14.51/μL vs 49.32 ± 6.41/μL, P < 0.05). Within monocyte subsets, hypoglycemia increased aggregation of intermediate monocytes (10.51 ± 1.42/μL vs euglycemia 4.19 ± 1.08/μL, P < 0.05; vs sham-saline 3.81± 1.42/μL, P < 0.05) and nonclassic monocytes (9.53 ± 1.08/μL vs euglycemia 2.86 ± 0.72/μL, P < 0.01; vs sham-saline 3.08 ± 1.01/μL, P < 0.05), with platelets compared with controls. Hypoglycemia led to greater leukocyte mobilization in response to subsequent low-dose endotoxin challenge (10.96 ± 0.97 vs euglycemia 8.21 ± 0.85 × 109/L, P < 0.05). Conclusions Hypoglycemia mobilizes monocytes, increases platelet reactivity, promotes interaction between platelets and proinflammatory monocytes, and potentiates the subsequent immune response to endotoxin. These changes may contribute to increased cardiovascular risk observed in people with diabetes.

scholarly journals Mecanismos de control neuroinmune y la vía colinérgica antiinflamatoria

Tequio ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 35-49
Author(s):  
Yobana Pérez-Cervera ◽  
Rafael Torres Rosas
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Diseases ◽  
Basic Research ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
First Line ◽  
Neuronal Mechanisms ◽  
Cholinergic Pathway ◽  
Pharmacological Control

The innate immune system is the first line of defense involved in protecting against external pathogens and is crucial for survival. However, uncontrolled activation of the immune system can result in more damage than the factor that triggered them, causing atrophic scarring, chronic inflammation and even Systemic inflammation events such as Lupus, arthritis, Crohn’s disease or sepsis. Fortunately, there are neuronal mechanisms of inflammatory control which could be part of new therapeutic strategies to be studied for a better control of this type of pathologies. In the last decade, the cholinergic pathway has been described as part of the neuronal mechanisms that can be exogenous activated for the non-pharmacological control of inflammatory diseases, the aim of this review is to present the evidence in basic research and encourage the research in medical practice.

scholarly journals Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses

2009 ◽  
Vol 29 (21) ◽  
pp. 5742-5750 ◽  
Author(s):  
Jess M. Cunnick ◽  
Sabine Schmidhuber ◽  
Gang Chen ◽  
Min Yu ◽  
Sun-Ju Yi ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Small Gtpase ◽  
Innate Immune ◽  
Ros Production ◽  
Activated Neutrophils ◽  
Inflammatory Processes ◽  
Null Mutant Mice

ABSTRACT Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes.

scholarly journals Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

2004 ◽  
Vol 2004 (3) ◽  
pp. 156-166 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Late Phase ◽  
Common Mechanism ◽  
Peroxisome Proliferator ◽  
Initiation Phase ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα,δ,γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases.

scholarly journals The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2991
Author(s):  
Lena M. Ernst ◽  
Eudald Casals ◽  
Paola Italiani ◽  
Diana Boraschi ◽  
Victor Puntes
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Inorganic Nanoparticles ◽  
Cellular Debris ◽  
Abnormal Cells ◽  
Nanoparticle Design ◽  
Modes Of Interaction ◽  
Molecular Patterns

The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design.

scholarly journals Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Hélène Duez ◽  
Benoit Pourcet
Keyword(s):  
Immune System ◽  
Nuclear Receptors ◽  
Nlrp3 Inflammasome ◽  
Innate Immune System ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Brain Diseases ◽  
Caspase 1

The innate immune system is the first line of defense specialized in the clearing of invaders whether foreign elements like microbes or self-elements that accumulate abnormally including cellular debris. Inflammasomes are master regulators of the innate immune system, especially in macrophages, and are key sensors involved in maintaining cellular health in response to cytolytic pathogens or stress signals. Inflammasomes are cytoplasmic complexes typically composed of a sensor molecule such as NOD-Like Receptors (NLRs), an adaptor protein including ASC and an effector protein such as caspase 1. Upon stimulation, inflammasome complex components associate to promote the cleavage of the pro-caspase 1 into active caspase-1 and the subsequent activation of pro-inflammatory cytokines including IL-18 and IL-1β. Deficiency or overactivation of such important sensors leads to critical diseases including Alzheimer diseases, chronic inflammatory diseases, cancers, acute liver diseases, and cardiometabolic diseases. Inflammasomes are tightly controlled by a two-step activation regulatory process consisting in a priming step, which activates the transcription of inflammasome components, and an activation step which leads to the inflammasome complex formation and the subsequent cleavage of pro-IL1 cytokines. Apart from the NF-κB pathway, nuclear receptors have recently been proposed as additional regulators of this pathway. This review will discuss the role of nuclear receptors in the control of the NLRP3 inflammasome and the putative beneficial effect of new modulators of inflammasomes in the treatment of inflammatory diseases including colitis, fulminant hepatitis, cardiac ischemia–reperfusion and brain diseases.

scholarly journals The Many Faces of Innate Immunity in SARS-CoV-2 Infection

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 596
Author(s):  
Nicholas Hanan ◽  
Ronnie L. Doud ◽  
In-Woo Park ◽  
Harlan P. Jones ◽  
Stephen O. Mathew
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
System A ◽  
Genetic Risks ◽  
Poor Outcomes ◽  
The Many ◽  
Lung Tissue Damage

The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia. Elevated interleukin (IL)-6 and IL-8 leads to overactivity and is a prominent feature of severe COVID-19 patients. IL-6 can result in lymphopenia; where COVID-19 patients typically have significantly altered lymphocyte subsets. IL-8 attracts neutrophils; which may play a significant role in lung tissue damage with the formation of neutrophil extracellular traps leading to cytokine storm or acute respiratory distress syndrome. Several factors like pre-existing co-morbidities, genetic risks, viral pathogenicity, and therapeutic efficacy act as important modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses. In this review, we discuss the role of the innate immune system at play with other important modifiers in SARS-CoV-2 infection.

scholarly journals Overlaps in the Pathogenesis of Rosacea and Atherosclerosis

2018 ◽  
Vol 72 (3) ◽  
pp. 152-159
Author(s):  
Aleksejs Zavorins ◽  
Jūlija Voicehovska ◽  
Jānis Ķīsis ◽  
Aivars Lejnieks
Keyword(s):  
Endoplasmic Reticulum ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Innate Immune System ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Inflammatory Skin Disease ◽  
Chronic Inflammatory Diseases ◽  
Central Regions ◽  
The Face

Abstract Rosacea is a chronic inflammatory skin disease characterised by transient or persistent erythema, telangiectasia, papules, and pustules that predominantly involve central regions of the face. Recent studies have shown a possible clinical association between rosacea and cardiovascular diseases (CVDs). Rosacea and atherosclerosis are both known to have alterations in the innate immune system, enhanced oxidative and endoplasmic reticulum stress. The aim of this review is to delve deep into the pathogenesis of rosacea and atherosclerosis to uncover possible pathogenic overlaps between these chronic inflammatory diseases.

scholarly journals NOD1 and NOD2 receptors: integral members of the innate and adaptive immunity system.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Halina Antosz ◽  
Magdalena Osiak
Keyword(s):  
Immune System ◽  
Signaling Pathways ◽  
Adaptive Immunity ◽  
Innate Immune System ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Inflammatory Signaling ◽  
Innate And Adaptive Immunity ◽  
Essential Component

NOD-like proteins (NLR) are a specialized group of intracellular receptors, which constitute an essential component of the host innate immune system. They were discovered more than a decade ago, but research on this particular class of microbial detectors is still ongoing to allow for a better understanding of the mechanisms, recognition of microorganisms, transmission of signals, and carrying out the activation of inflammatory signaling pathways. In this review, we discuss the construction of NOD1 and NOD2 receptors, their functions, and significance in the pathogenesis of inflammatory diseases in humans.

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