scholarly journals MiR-486-3p and MiR-938—Important Inhibitors of Pacemaking Ion Channels and/or Markers of Immune Cells

2021 ◽  
Vol 11 (23) ◽  
pp. 11366
Author(s):  
Abimbola J Aminu ◽  
Maria Petkova ◽  
Weixuan Chen ◽  
Zeyuan Yin ◽  
Vlad S Kuzmin ◽  
...  
Keyword(s):  
Ion Channels ◽  
Mast Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Luciferase Activity ◽  
Sinus Node ◽  
Luciferase Assay ◽  
Potential Therapeutic Target ◽  
The Right

The sinus node (SN) is the heart’s primary pacemaker and has a unique expression of pacemaking ion channels and immune cell markers. The role of microribonucleic acids (miRNAs) in control of ion channels and immune function of the sinus node is not well understood. We have recently shown that hsa-miR-486-3p downregulates the main pacemaking channel HCN4 in the SN. In addition, we recently demonstrated that immune cells are significantly more abundant in the SN compared to the right atrium. The aim of this study was to validate the previously predicted interactions between miRNAs and mRNAs of key Ca2+ ion channels (involved in peacemaking) and mRNA of TPSAB1—(a mast cells marker) using luciferase assay. We now show that miR-486 significantly downregulates Cav1.3, Cav3.1, and TPSAB1-mediated luciferase activity, while miR-938 significantly downregulates only TPSAB1-mediated luciferase activity. This makes miR-486-3p a potential therapeutic target in the treatment of SN dysfunctions.

The Role of TRP Channels in Allergic Inflammation and its Clinical Relevance

2020 ◽  
Vol 27 (9) ◽  
pp. 1446-1468 ◽  
Author(s):  
Joo Hyun Nam ◽  
Woo Kyung Kim
Keyword(s):  
T Cells ◽  
Ion Channels ◽  
Mast Cells ◽  
Immune Cells ◽  
Trp Channels ◽  
Allergic Inflammation ◽  
Current Status ◽  
Calcium Signal ◽  
Trp Ion Channels

Allergy refers to an abnormal adaptive immune response to non-infectious environmental substances (allergen) that can induce various diseases such as asthma, atopic dermatitis, and allergic rhinitis. In this allergic inflammation, various immune cells, such as B cells, T cells, and mast cells, are involved and undergo complex interactions that cause a variety of pathophysiological conditions. In immune cells, calcium ions play a crucial role in controlling intracellular Ca2+ signaling pathways. Cations, such as Na+, indirectly modulate the calcium signal generation by regulating cell membrane potential. This intracellular Ca2+ signaling is mediated by various cation channels; among them, the Transient Receptor Potential (TRP) family is present in almost all immune cell types, and each channel has a unique function in regulating Ca2+ signals. In this review, we focus on the role of TRP ion channels in allergic inflammatory responses in T cells and mast cells. In addition, the TRP ion channels, which are attracting attention in clinical practice in relation to allergic diseases, and the current status of the development of therapeutic agents that target TRP channels are discussed.

Role of sinoatrial ring bundle in internodal conduction

1976 ◽  
Vol 231 (2) ◽  
pp. 319-325 ◽  
Author(s):  
M Hiraoka ◽  
T Sano
Keyword(s):  
Sinus Node ◽  
The Other ◽  
Wave Fronts ◽  
Av Node ◽  
Crista Terminalis ◽  
Main Route ◽  
Endocardial Surface ◽  
The Right ◽  
Activation Sequence

The role of the sinoatrial ring bundle (SARB) in internodal conduction was examined by the microelectrode technique in excised rabbit hearts. The spread of the sinus impluse to the surrounding tissues was shown to proceed anteriorly toward the right branch of the crista terminalis significantly faster than toward the other direction. Thus the right SARB and the right branch of the crista terminalis close to the sinus node were the earliest areas excited by the sinus impulse in the areas surrounding the sinus node. It was further shown that the activation sequence does not initiate from the right SARB to the right branch of the crista terminalis via the junction of these two structures. Cutting the SARB did not produce any delay in conduction from the sinus node to the atrioventricular (AV) node. The conduction velocity measured at the endocardial surface by two microelectrodes has proved that conduction in the crista terminalis was significantly faster than in the SARB. The upstroke of the action potential from the crista terminalis was also steeper than that from the SARB. These results suggest that the SARB is not the main route for impulse propagation from the sinus node to the AV node; the fastest internodal conduction therefore takes place with wide wave fronts, along the crista terminalis.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

scholarly journals Immune cell-specific Cre reporter mouse labels a subset of CNS neurons

2019 ◽  
Author(s):  
Aurélie Bouteau ◽  
Botond Z. Igyártó
Keyword(s):  
Immune Cells ◽  
Langerhans Cells ◽  
Immune Cell ◽  
Neuronal Marker ◽  
Reporter Mouse ◽  
Cns Neurons ◽  
The Central Nervous System ◽  
Antigen Presenting

AbstractHuLangerin-Cre-YFPf/f mice were generated to specifically mark a subset of antigen presenting immune cells, called Langerhans cells (LCs). During histological characterization of these mice, we found that, in addition to LCs an uncharacterized cell population in the central nervous system (CNS) also expressed YFP. In this study, we found that the CNS YFP+ cells were negative for microglia and astrocyte markers, but they expressed mature neuronal marker NeuN and showed neuronal localization/morphology. Thus, these mice might be used to study the ontogeny, migration and the role of a subset of CNS neurons.

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zuojun Zhang ◽  
Ming Zhao ◽  
Guojie Wang
Keyword(s):  
Luciferase Activity ◽  
Bioinformatic Analysis ◽  
Luciferase Assay ◽  
Circular Rnas ◽  
Potential Biomarker ◽  
Luciferase Activity Assay ◽  
Proliferation And Metastasis ◽  
Normal Controls ◽  
Tgf Β1

Abstract Background Osteosarcoma is a most common bone malignant tumor which threatens children and adolescents. Circular RNAs (circRNAs) fundamentally play essential roles in the progress and development of human cancers by sponging with microRNAs (miRNAs). However, the role of circRNAs in osteosarcoma is not clear. The aim of the study was to investigate the roles and molecular mechanism of circRNAs in osteosarcoma. Results The data from qRT-PCR showed that circ_0051079 expression was higher in osteosarcoma cells and tissues compared to their normal controls. Meanwhile, bioinformatic analysis indicated that circ_0051079 was a sponge of miR-26a-5p, which was verified by luciferase activity assay. Subsequently, TGF-β1 was verified as a putative target mRNA of miR-26a-5p by luciferase assay. Cellular function assays were conducted and the findings revealed that circ_0051079/miR-26a-5p/TGF-β1 regulated osteosarcoma proliferation and metastasis. Conclusion The study demonstrated that circ_0051079 could act as an oncogene via regulating miR-26a-5p/TGF-β1 and a potential biomarker for osteosarcoma diagnose.

scholarly journals Impaired FcϵRI stability, signaling, and effector functions in murine mast cells lacking glycosylphosphatidylinositol-anchored proteins

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4377-4383 ◽  
Author(s):  
Wouter L. W. Hazenbos ◽  
Ping Wu ◽  
Jeffrey Eastham-Anderson ◽  
Taroh Kinoshita ◽  
Eric J. Brown
Keyword(s):  
Mast Cells ◽  
Targeted Disruption ◽  
Potential Therapeutic Target ◽  
Effector Functions ◽  
Ige Mediated ◽  
Interchain Interactions ◽  
Β Chain ◽  
Stimulation Of

Abstract A key event and potential therapeutic target in allergic and asthmatic diseases is signaling by the IgE receptor FcϵRI, which depends on its interactions with Src family kinases (SFK). Here we tested the hypothesis that glycosylphosphatidylinositiol-anchored proteins (GPI-AP) are involved in FcϵRI signaling, based on previous observations that GPI-AP colocalize with and mediate activation of SFK. We generated mice with a hematopoietic cell-specific GPI-AP deficiency by targeted disruption of the GPI biosynthesis gene PigA. In these mice, IgE-mediated passive cutaneous anaphylaxis was largely abolished. PigA-deficient mast cells cultured from these mice showed impaired degranulation in response to stimulation with IgE and antigen in vitro, despite normal IgE binding and antigen-induced FcϵRI aggregation. On stimulation of these cells with IgE and antigen, coprecipitation of the FcϵRI α-chain with the γ-chain and β-chain was markedly reduced. As a result, IgE/antigen–induced FcϵRI-Lyn association and γ-chain tyrosine phosphorylation were both impaired in PigA-deficient cells. These data provide genetic evidence for an unanticipated key role of GPI-AP in FcϵRI interchain interactions and early FcϵRI signaling events, necessary for antigen-induced mast cell degranulation.

scholarly journals Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD+/nicotinamide

2019 ◽  
Vol 116 (14) ◽  
pp. 2226-2238 ◽  
Author(s):  
Tetsuo Horimatsu ◽  
Andra L Blomkalns ◽  
Mourad Ogbi ◽  
Mary Moses ◽  
David Kim ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Aortic Aneurysms ◽  
Cell Infiltration ◽  
Protective Effects ◽  
Abdominal Aortic ◽  
G Protein Coupled

Abstract Aims Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. Methods and results Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. Conclusion Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

scholarly journals Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 269 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Fayek Ahmad ◽  
Afsar Raza Naqvi
Keyword(s):  
Cell Differentiation ◽  
Immune Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Immune Cell ◽  
Lymphoid Cells ◽  
Tissue Cell ◽  
Specific Expression ◽  
And Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

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