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 The Role of GPNMB in Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Marina Saade ◽  
Giovanna Araujo de Souza ◽  
Cristoforo Scavone ◽  
Paula Fernanda Kinoshita
Keyword(s):  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Published Evidence ◽  
The Central Nervous System ◽  
Inflammation Resolution ◽  
The Brain ◽  
Lps Treatment

Inflammation is a response to a lesion in the tissue or infection. This process occurs in a specific manner in the central nervous system and is called neuroinflammation, which is involved in neurodegenerative diseases. GPNMB, an endogenous glycoprotein, has been recently related to inflammation and neuroinflammation. GPNMB is highly expressed in macrophages and microglia, which are cells involved with innate immune response in the periphery and the brain, respectively. Some studies have shown increased levels of GPNMB in pro-inflammatory conditions, such as LPS treatment, and in pathological conditions, such as neurodegenerative diseases and cancer. However, the role of GPNMB in inflammation is still not clear. Even though most studies suggest that GPNMB might have an anti-inflammatory role by promoting inflammation resolution, there is evidence that GPNMB could be pro-inflammatory. In this review, we gather and discuss the published evidence regarding this interaction.

Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the bradykinin B2 receptor

2003 ◽  
Vol 284 (6) ◽  
pp. H1904-H1908 ◽  
Author(s):  
Joost P. Schanstra ◽  
Johan Duchene ◽  
Françoise Praddaude ◽  
Patrick Bruneval ◽  
Ivan Tack ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Renal Hemodynamics ◽  
Wild Type ◽  
Kidney Fibrosis ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Induced Hypertension ◽  
Free Environment ◽  
Glomerular Tuft

Bradykinin B2 receptor knockout mice (B2 −/−) have been useful to study the role of bradykinin under pathological conditions. With the use of these mice, it was shown that bradykinin plays an important role in angiogenesis, heart failure, salt-induced hypertension, and kidney fibrosis. Data on the role of the bradykinin B2 receptor under physiological conditions using these mice are controversial and scarce, because these mice have no typical phenotype. For this reason, we have studied, under physiological conditions, renal hemodynamics as well as a number of morphometric glomerular parameters of B2 −/− mice on a homogenized genetic background and on mice bred in a pathogen-free environment. Backcrossed B2 −/− mice had normal blood pressure and normal apparent renal hemodynamics and morphology. However, reduced renal nitrite excretion and glomerular cGMP content were found, which was associated with a reduced glomerular capillary surface area. These differences had, however, no detectable effects on renal hemodynamics. These differences between B2 −/− and wild-type mice might become important under pathological conditions as shown by a number of studies using these bradykinin B2 receptor knockout mice.

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 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 Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Francesco Sabbatino ◽  
Valeria Conti ◽  
Luigi Liguori ◽  
Giovanna Polcaro ◽  
Graziamaria Corbi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Ros Production ◽  
Oxygen Species ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Detoxification Systems ◽  
Cancer Diseases

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.

scholarly journals Heparanase: A Multitasking Protein Involved in Extarcellular Matrix (ECM) Remodeling and Cellular Signaling

2018 ◽  
Author(s):  
Valentina Masola ◽  
Gloria Bellin ◽  
Giovanni Gambaro ◽  
Maurizio Onisto
Keyword(s):  
Enzymatic Activity ◽  
Normal Tissue ◽  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Ecm Remodeling ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Low Levels ◽  
And Diffusion

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules as growth factors, cytokines and enzymes. In addition to being an enzyme HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on current knowledge about the different role of HPSE protein exerted by its enzymatic and not-enzymatic activity.

scholarly journals The role of eicosanoids in renal diseases – potential therapeutic possibilities

2018 ◽  
Author(s):  
Maciej Fijałkowski ◽  
Joanna Stępniewska ◽  
Maciej Domański ◽  
Kazimierz Ciechanowski ◽  
Edyta Golembiewska
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Biologically Active ◽  
Renal Diseases ◽  
Membrane Phospholipids ◽  
Future Studies ◽  
Renal Replacement Therapies ◽  
Pathological Conditions ◽  
Inflammatory Processes

Eicosanoids are biologically active molecules that are created in the process of oxidation of arachidonic acid (AA) which is a constituent of the cell membrane phospholipids. Throughout the years it was evidenced by experiments that the lipid and lipid-derived metabolites play an important role in physiological and pathological processes in the kidneys. They are being considered as biomarkers in detecting acute kidney injury, nephrotoxicity, glomerulonephritis and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress. They might be also considered as potential novel targets of therapy. However, the role of eicosanoids is still not fully clear and needs to be explored in future studies. In this brief review, studies on the role of eicosanoids in physiological and pathological conditions, e.g. acute kidney injury (AKI) and chronic kidney disease (CKD), and in different renal replacement therapies, including kidney transplantation, are being discussed.

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 Endothelial dysfunction in context of women’s health disorders from menarche to menopause

2020 ◽  
Vol 4 (33) ◽  
pp. 6-14
Author(s):  
I. V. Kuznetsova
Keyword(s):  
Endothelial Dysfunction ◽  
Drug Group ◽  
Female Population ◽  
Physiological Conditions ◽  
The Past ◽  
Vascular Bed ◽  
Pathological Conditions ◽  
Wide Range ◽  
Timely Treatment

Endothelial function is an essential component of providing homeostasis, which allows controlling the state of the vascular bed and ensuring blood supply to organs both under physiological conditions and under the influence of various damaging factors. Endothelial dysfunction is associated with a wide range of pathological conditions and diseases, in the pathogenesis of which the vascular link is involved. Understanding the unifying role of endothelial dysfunction in the pathology of different fields of medicine allows, firstly, to predict the development of serious socially significant diseases, such as cardiovascular diseases, which remain the main cause of death among women. In particular, over the past decade, several cardiovascular risk factors specific to the female population have been identified, such as hypertensive pregnancy complications and menopausal vasomotor symptoms, which, in turn, are caused by endothelial dysfunction. Secondly, timely treatment of endotheliosis suspends or completely prevents both transient disorders associated with endothelial dysfunction and their serious consequences. In this regard, the drug group of glycosaminoglycans and its representative sulodexide are of interest.

scholarly journals Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology

2021 ◽  
Vol 11 ◽  
Author(s):  
Antoine Duquette ◽  
Camille Pernègre ◽  
Ariane Veilleux Carpentier ◽  
Nicole Leclerc
Keyword(s):  
Protein A ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation ◽  
Therapeutic Approaches ◽  
Tau Pathology ◽  
Physiological Conditions ◽  
The Third ◽  
Pathological Conditions ◽  
The Brain

Tau protein, a neuronal microtubule-associated protein, becomes hyperphosphorylated in several neurodegenerative diseases called tauopathies. Hyperphosphorylation of tau is correlated to its redistribution from the axon to the somato-dendritic compartment at early stages of tauopathies. Interestingly, tau hyperphosphorylation begins in different regions of the brain in each tauopathy. In some regions, both neurons and glial cells develop tau hyperphosphorylation. Tau hyperphosphorylation is also observed in physiological conditions such as hibernation and brain development. In the first section of present article, we will review the spatiotemporal and cellular distribution of hyperphosphorylated tau in the most frequent tauopathies. In the second section, we will compare the pattern of tau hyperphosphorylation in physiological and pathological conditions and discuss the sites that could play a pivotal role in the conversion of non-toxic to toxic forms of hyperphosphorylated tau. Furthermore, we will discuss the role of hyperphosphorylated tau in physiological and pathological conditions and the fact that tau hyperphosphorylation is reversible in physiological conditions but not in a pathological ones. In the third section, we will speculate how the differences and similarities between hyperphosphorylated tau in physiological and pathological conditions could impact the elaboration of therapies to prevent tau pathology. In the fourth section, the different therapeutic approaches using tau as a direct or indirect therapeutic target will be presented.

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