scholarly journals The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mohsin H. K. Roshan ◽  
Amos Tambo ◽  
Nikolai P. Pace
Keyword(s):  
Adaptor Protein ◽  
Arterial Disease ◽  
Primary Response ◽  
Atheromatous Plaque ◽  
Nf Kappa B ◽  
Coronary Arterial Disease ◽  
Inflammatory Conditions ◽  
Inflammatory Processes ◽  
Molecular Patterns

Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/−and TLR4−/−mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α(INF-α) secretion and increases cytotoxic activity of CD4+T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease.

scholarly journals Brain natriuretic peptide: Diagnostic potential in dogs

2009 ◽  
Vol 63 (5-6) ◽  
pp. 381-392
Author(s):  
Ljubica Spasojevic-Kosic
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Arterial Disease ◽  
Cardiac Insufficiency ◽  
Everyday Clinical Practice ◽  
Coronary Arterial Disease ◽  
Diagnostic Potential ◽  
Adequate Method

The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP) has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

scholarly journals Role of Toll-Interacting Protein Gene Polymorphisms in Leprosy Mexican Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Margarita Montoya-Buelna ◽  
Mary Fafutis-Morris ◽  
Alvaro J. Tovar-Cuevas ◽  
Anabell Alvarado-Navarro ◽  
Yeminia Valle ◽  
...  
Keyword(s):  
Adaptor Protein ◽  
Lepromatous Leprosy ◽  
Microbial Pathogens ◽  
Specific Primers ◽  
Interacting Protein ◽  
Hardy Weinberg Equilibrium ◽  
Genotype C ◽  
Molecular Patterns ◽  
Mexican Patients

Background. Leprosy is a debilitating infectious disease of human skin and nerves. Genetics factors of the host play an important role in the disease susceptibility. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, which recognizes structurally conserved molecular patterns of microbial pathogens, initiating immune responses. The objective of this study was to investigate the association of variants in theTOLLIPgene with susceptibility to leprosy in Mexican patients.Methods.TOLLIPpolymorphisms were studied using a case-control design of Mexican patients with lepromatous leprosy (LL). The polymorphisms ofTOLLIPat loci −526 C>G (rs5743854), 1309956C>T (rs3750920), 1298430C>A (rs5744015), and 1292831 G>A (rs3750919) were analyzed by PCR, with sequence-specific primers in LL patients and healthy subjects (HS) as controls.Results. Genotype distributions were in Hardy Weinberg equilibrium for all sites except for rs3750920. Neither genotype nor allele frequencies were statistically different between LL patients and controls (P>0.05). The maximum pairwise D’ coefficient reached was 0.44 of linkage (P=0.01) for all the polymorphisms except for rs5743854. The three loci haplotype comparison yielded no significant differences between groups.Conclusions. Just the individuals with genotype C/C of rs3750920 have a trend of protective effect to developing LL.

scholarly journals Tackling Chronic Pain and Inflammation through the Purinergic System

2018 ◽  
Vol 25 (32) ◽  
pp. 3830-3865 ◽  
Author(s):  
Giulia Magni ◽  
Daniele Riccio ◽  
Stefania Ceruti
Keyword(s):  
Membrane Transporters ◽  
Receptor Subtypes ◽  
Physiological Conditions ◽  
Purinergic System ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Inflammatory Processes ◽  
Clear Identification ◽  
The Many

The purinergic system is composed of purine and pyrimidine transmitters, the enzymes that modulate the interconversion of nucleotides and nucleosides, the membrane transporters that control their extracellular concentrations, and the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.

scholarly journals Role of microRNAs in the Regulation of Dendritic Cell Generation and Function

2020 ◽  
Vol 21 (4) ◽  
pp. 1319 ◽  
Author(s):  
Viviana Scalavino ◽  
Marina Liso ◽  
Grazia Serino
Keyword(s):  
Adaptive Systems ◽  
Intrinsic Factors ◽  
Inflammatory Conditions ◽  
Inflammatory Processes ◽  
Plasmacytoid Dcs ◽  
Non Coding Rnas ◽  
And Function ◽  
Antigen Presenting ◽  
Mirna Deregulation

Dendritic cells (DCs) are antigen-presenting cells with a key role in immune responses. They act as a link between the innate and adaptive systems and they can induce and maintain immunologic tolerance. DCs are subdivided into conventional and plasmacytoid DCs. These cell subsets originate from the same bone marrow precursors and their differentiation process is determined by several extrinsic and intrinsic factors, such as cytokines, transcription factors, and miRNAs. miRNAs are small non-coding RNAs that play a crucial role in modulating physiological and pathological processes mediated by DCs. miRNA deregulation affects many inflammatory conditions and diseases. The aim of this review was to underline the importance of miRNAs in inflammatory processes mediated by DCs in physiological and pathological conditions and to highlight their potential application for future therapies.

scholarly journals Inflammatory Mediators in Vascular Disease: Identifying Promising Targets for Intracranial Aneurysm Research

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
David M. Sawyer ◽  
Peter S. Amenta ◽  
Ricky Medel ◽  
Aaron S. Dumont
Keyword(s):  
Intracranial Aneurysm ◽  
Intracranial Aneurysms ◽  
Future Research ◽  
Specific Interactions ◽  
Effector Molecules ◽  
Inflammatory Processes ◽  
And Function ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Inflammatory processes are implicated in many diseases of the vasculature and have been shown to play a key role in the formation of intracranial aneurysms (IAs). Although the specific mechanisms underlying these processes have been thoroughly investigated in related pathologies, such as atherosclerosis, there remains a paucity of information regarding the immunopathology of IA. Cells such as macrophages and lymphocytes and their effector molecules have been suggested to be players in IA, but their specific interactions and the role of other components of the inflammatory response have yet to be determined. Drawing parallels between the pathogenesis of IA and other vascular disorders could provide a roadmap for developing a mechanistic understanding of the immunopathology of IA and uncovering useful targets for therapeutic intervention. Future research should address the presence and function of leukocyte subsets, mechanisms of leukocyte recruitment and activation, and the role of damage-associated molecular patterns in IA.

The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques

2017 ◽  
Vol 95 (10) ◽  
pp. 1245-1253 ◽  
Author(s):  
Vikrant Rai ◽  
Devendra K. Agrawal
Keyword(s):  
High Mobility ◽  
Interferon Γ ◽  
Chronic Inflammatory Disease ◽  
Plaque Formation ◽  
Atheromatous Plaque ◽  
Surface Receptors ◽  
Downstream Signaling ◽  
Stable Plaque ◽  
Molecular Patterns

Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll-like receptors and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, IL-6, and interferon-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.

scholarly journals Cross-Talk of Atherosclerosis and Ischemic Stroke: Dramatic Role of Neutrophils

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Abdolreza Esmaeilzadeh ◽  
Maryam Zarerafie ◽  
Azita Mohammadzadeh
Keyword(s):  
Ischemic Stroke ◽  
Cross Talk ◽  
Interleukin 1 ◽  
Primary Response ◽  
Toll Like Receptor 4 ◽  
Inflammatory Microenvironment ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Necrosis Factor

Context: Current investigations illustrate the increasing prevalence of atherosclerosis (AS) through the aggravating role of inappropriate lifestyle patterns. Atherosclerosis is the cause of important vascular-related diseases such as ischemic stroke (IS). Understanding AS pathophysiology can help reduce the incidence of AS-mediated diseases like ischemic stroke. Evidence Acquisition: For this narrative review article, we used the five mega databases of PubMed, Google Scholar, Scopus, Springer, and Science Direct. We searched from 2010 Jan to 2020 Dec and based on keywords and inclusion criteria, 77 articles were enrolled. Results: Based on prior articles on atherosclerosis and ischemic stroke pathophysiology, local and systemic inflammation is a vigorous factor in both diseasesIndeed, the fundamental inflammatory pathway involved atherosclerosis, and ischemic stroke is associated with the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-kappa B (TLR4/ Myd88/ NF-κB) cascade. The functional paw of these intricate mechanisms are pro-inflammatory mediators, such as interleukin-1 beta (IL-1β), tumor necrosis factor (TNF-α), and interleukin-18 (IL-18) incite inflammation. Besides, the essential structures termed inflammasomes (multi proteins components), and multiplicity of immune and non-immune cells (i.e., neutrophils, monocytes, platelets, and macrophages) are beneficial in the induction of inflammatory microenvironment. Conclusions: Neutrophils could be the most effective cells in the inflammation-based mechanism in IS and AS. It is clarified that neutrophils with the recruitment of own vesicles and granules can afford to amplify inflammatory conditions and be a key cell in AS and IS cross-talk. Therefore, utilizing methods to control neutrophils-mediated mechanisms could be an effective method for the prevention of AS and IS.

scholarly journals Interleukin-36 Cytokines in Infectious and Non-Infectious Lung Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hernán F. Peñaloza ◽  
Rick van der Geest ◽  
Joel A. Ybe ◽  
Theodore J. Standiford ◽  
Janet S. Lee
Keyword(s):  
Infectious Diseases ◽  
Lung Diseases ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inflammatory Conditions ◽  
Inflammatory Processes

The IL-36 family of cytokines were identified in the early 2000’s as a new subfamily of the IL-1 cytokine family, and since then, the role of IL-36 cytokines during various inflammatory processes has been characterized. While most of the research has focused on the role of these cytokines in autoimmune skin diseases such as psoriasis and dermatitis, recent studies have also shown the importance of IL-36 cytokines in the lung inflammatory response during infectious and non-infectious diseases. In this review, we discuss the biology of IL-36 cytokines in terms of how they are produced and activated, as well as their effects on myeloid and lymphoid cells during inflammation. We also discuss the role of these cytokines during lung infectious diseases caused by bacteria and influenza virus, as well as other inflammatory conditions in the lungs such as allergic asthma, lung fibrosis, chronic obstructive pulmonary disease, cystic fibrosis and cancer. Finally, we discuss the current therapeutic advances that target the IL-36 pathway and the possibility to extend these tools to treat lung inflammatory diseases.

scholarly journals Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala

2019 ◽  
Vol 9 (12) ◽  
pp. 361 ◽  
Author(s):  
Michal Bajo ◽  
Reesha R. Patel ◽  
David M. Hedges ◽  
Florence P. Varodayan ◽  
Roman Vlkolinsky ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Motor Coordination ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Gaba Release ◽  
Primary Response ◽  
Central Amygdala ◽  
Gabaergic Transmission ◽  
Whole Cell Patch Clamp

Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically MyD88 regulates ethanol drinking, ethanol-induced sedation, and ethanol-induced deficits in motor coordination. In this study, we examined the role of MyD88 in mediating the effects of IL-1β and ethanol on GABAergic transmission in the central amygdala (CeA) of male mice using whole-cell patch-clamp recordings in combination with pharmacological (AS-1, a mimetic that prevents MyD88 recruitment by IL-1R) and genetic (Myd88 knockout mice) approaches. We demonstrate through both approaches that IL-1β and ethanol’s modulatory effects at CeA GABA synapses are not dependent on MyD88. Myd88 knockout potentiated IL-1β’s actions in reducing postsynaptic GABAA receptor function. Pharmacological inhibition of MyD88 modulates IL-1β’s action at CeA GABA synapses similar to Myd88 knockout mice. Additionally, ethanol-induced CeA GABA release was greater in Myd88 knockout mice compared to wildtype controls. Thus, MyD88 is not essential to IL-1β or ethanol regulation of CeA GABA synapses but plays a role in modulating the magnitude of their effects, which may be a potential mechanism by which it regulates ethanol-related behaviors.

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