scholarly journals Exosomes: Mechanisms of Uptake

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Kelly J. McKelvey ◽  
Katie L. Powell ◽  
Anthony W. Ashton ◽  
Jonathan M. Morris ◽  
Sharon A. McCracken
Keyword(s):  
Autoimmune Diseases ◽  
Cancer Cells ◽  
Pregnancy Complications ◽  
Cellular Response ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Signalling Pathways ◽  
Exosome Biogenesis

Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells) and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.

scholarly journals Regulation of Energy Expenditure and Brown/Beige Thermogenic Activity by Interleukins: New Roles for Old Actors

2018 ◽  
Vol 19 (9) ◽  
pp. 2569 ◽  
Author(s):  
María García ◽  
Patricia Pazos ◽  
Luis Lima ◽  
Carlos Diéguez
Keyword(s):  
Energy Expenditure ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Molecular Switches ◽  
Metabolic Effects ◽  
Signalling Pathways ◽  
Functional Heterogeneity ◽  
Beige Adipocytes ◽  
The Central Nervous System ◽  
And Function

Obesity rates and the burden of metabolic associated diseases are escalating worldwide Energy burning brown and inducible beige adipocytes in human adipose tissues (ATs) have attracted considerable attention due to their therapeutic potential to counteract the deleterious metabolic effects of nutritional overload and overweight. Recent research has highlighted the relevance of resident and recruited ATs immune cell populations and their signalling mediators, cytokines, as modulators of the thermogenic activity of brown and beige ATs. In this review, we first provide an overview of the developmental, cellular and functional heterogeneity of the AT organ, as well as reported molecular switches of its heat-producing machinery. We also discuss the key contribution of various interleukins signalling pathways to energy and metabolic homeostasis and their roles in the biogenesis and function of brown and beige adipocytes. Besides local actions, attention is also drawn to their influence in the central nervous system (CNS) networks governing energy expenditure.

scholarly journals The Number and Position of Orai3 Units within Heteromeric Store-Operated Ca2+ Channels Alter the Pharmacology of ICRAC

2020 ◽  
Vol 21 (7) ◽  
pp. 2458 ◽  
Author(s):  
Sven Kappel ◽  
Tatiana Kilch ◽  
Roland Baur ◽  
Martin Lochner ◽  
Christine Peinelt
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Immune Cell ◽  
Outward Current ◽  
Cell Types ◽  
Prostate Cancer Cells ◽  
Channel Change ◽  
Outward Currents ◽  
Patch Clamp Electrophysiology ◽  
Ca2 Channels

Store-operated heteromeric Orai1/Orai3 channels have been discussed in the context of aging, cancer, and immune cell differentiation. In contrast to homomeric Orai1 channels, they exhibit a different pharmacology upon application of reactive oxygen species (ROS) or 2-aminoethoxydiphenyl borate (2-APB) in various cell types. In endogenous cells, subunit composition and arrangement may vary and cannot be defined precisely. In this study, we used patch-clamp electrophysiology to investigate the 2-APB profile of store-operated and store-independent homomeric Orai1 and heteromeric Orai1/Orai3 concatenated channels with defined subunit compositions. As has been shown previous, one or more Orai3 subunit(s) within the channel result(s) in decreased Ca2+ release activated Ca2+ current (ICRAC). Upon application of 50 µM 2-APB, channels with two or more Orai3 subunits exhibit large outward currents and can be activated by 2-APB independent from storedepletion and/or the presence of STIM1. The number and position of Orai3 subunits within the heteromeric store-operated channel change ion conductivity of 2-APB-activated outward current. Compared to homomeric Orai1 channels, one Orai3 subunit within the channel does not alter 2-APB pharmacology. None of the concatenated channel constructs were able to exactly simulate the complex 2-APB pharmacology observed in prostate cancer cells. However, 2-APB profiles of prostate cancer cells are similar to those of concatenated channels with Orai3 subunit(s). Considering the presented and previous results, this indicates that distinct subtypes of heteromeric SOCE channels may be selectively activated or blocked. In the future, targeting distinct heteromeric SOCE channel subtypes may be the key to tailored SOCE-based therapies.

Human FcγRIII (CD16) Polymorphism Screening Is Enhanced with Pyrosequencing Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4911-4911
Author(s):  
Ksenia Matlawska-Wasowska ◽  
James Gale ◽  
Parisa Khalili ◽  
Bridget S Wilson ◽  
Mohammad Vasef ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Targeted Therapies ◽  
Nested Pcr ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Therapeutic Potential ◽  
Allelic Polymorphism ◽  
Allele Specific ◽  
Specific Restriction

Abstract Abstract 4911 Surface specific antigens expressed on the cell membrane of hematopoietic cells are attractive target for antibody mediated cancer cells therapy. Monoclonal antibodies involve various mechanisms to eliminate cancer cells, including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) mediated by immune effector cells such as NK cells and macrophages bearing FcγRIIIA (CD16) receptor. Previous studies reported that clinical efficacy of monoclonal antibodies can be linked to the single nucleotide polymorphism found at position 559 in cDNA of the gene encoding FcγRIIIA. This allelic polymorphism generateses the following allotypes V/V, F/V or F/F at amino acid position 158 and can affect binding of mAbs and immune cell effector function. CD16-mediated binding is most efficient with the V/V genotype, and least efficient with the F/F genotype, leading to a range of efficacy in mAb-mediated targeted therapies. Currently, many patients are not screened for CD16 heterozygosity. Nevertheless there is a clear need for a diagnostic assay that will allow estimating the allelic polymorphism of a patient undergoing treatment with monoclonal antibodies utilizing ADCC/ADCP. Here we hypothesized that the pyrosequencing might improve a screening for polymorphisms of human FcγRIIIA-158 receptor. We studied 42 normal human subjects for the incidence of V/V, F/V and F/F CD16 polymorphisms using pyrosequencing technologies and compared to nested PCR-based allele-specific restriction assay. Compared to pyrosequencing, the nested PCR-based allele-specific restriction assay was 0. 33 sensitive and 1. 0 specific in discriminating the V/V and F/F genotypes, and 0. 33 sensitive and 0. 7 specific for the V/V and F/V genotypes (Table 1). Compared to pyrosequencing, the nested PCR-based allele-specific restriction assay was relatively insensitive and not specific in distinguishing the V/V genotype from other genotypes. Since the efficacy of the mAb-based targeted immunotherapy may be highly dependent upon the CD16 polymorphism in any given individual, we propose that pyrosequencing of the CD16 receptor be routinely evaluated in all patients. Such practices might prevent patients from randomizing to receive targeted therapies to that hematological malignancies for that have little or no therapeutic potential. Table 1 V/V F/V F/F pyrosequencing 6 16 20 allele-specific restriction assay 2 23 17 sensitivity - 0.33 0.33 specificity - 0.7 1.0 Disclosures: No relevant conflicts of interest to declare.

Therapeutic potential of galectin-1 and galectin-3 in autoimmune diseases

2021 ◽  
Vol 27 ◽  
Author(s):  
Yi-Sheng He ◽  
Yu-Qian Hu ◽  
Kun Xiang ◽  
Yue Chen ◽  
Ya-Ting Feng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Vital Role ◽  
Promising Therapeutic Target ◽  
Galectin 3

: Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. It can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies indicate that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. These information may provide a novel and promising therapeutic target for autoimmune diseases.

Green tea EGCG, T-cell function, and T-cell-mediated autoimmune encephalomyelitis

2016 ◽  
Vol 64 (8) ◽  
pp. 1213-1219 ◽  
Author(s):  
Dayong Wu
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Green Tea ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Lymphoid Tissues ◽  
Autoimmune Encephalomyelitis ◽  
Cell Functions

Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to modulate immune cell functions and improve some autoimmune diseases in animal models. In a series of studies we determined EGCG's effect on T-cell functions and its application in autoimmune diseases. We first observed that EGCG inhibited CD4+T-cell expansion induced by polyclonal (mitogens or anti-CD3/CD28) or antigen-specific stimulation. We then showed that EGCG suppressed expansion and cell cycle progression of naïve CD4+T by modulating cell cycle-related proteins. EGCG also inhibited naive CD4+T-cell differentiation into Th1 and Th17 effector subsets by impacting their respective signaling transducers and transcription factors. These results suggest that EGCG may improve T-cell-mediated autoimmune diseases. Using the experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis, we found that dietary supplementation with EGCG attenuated the disease's symptoms and pathology. These EGCG-induced changes are associated with findings in the immune and inflammation profiles in lymphoid tissues and the central nervous system: a reduction in proliferation of autoreactive T cells, production of proinflammatory cytokines, and Th1 and Th17 subpopulations, and an increase in regulatory T-cell populations. These results suggest that green tea or its active components may have a preventive and therapeutic potential in dealing with T-cell-mediated autoimmune diseases. However, the translational value of these findings needs to be validated in future human studies.

scholarly journals Exosomes and Micro-RNAs in Aging Process

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 968
Author(s):  
Yousra Hamdan ◽  
Loubna Mazini ◽  
Gabriel Malka
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Fluids ◽  
Cell Types ◽  
Exosome Biogenesis ◽  
Age Related ◽  
Micro Rnas ◽  
Underlying Mechanisms ◽  
Almost All

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.

scholarly journals P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2098 ◽  
Author(s):  
Virginie Aires ◽  
Didier J Colin ◽  
Agnès Doreau ◽  
Attilio Di Pietro ◽  
Jean-Marie Heydel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cellular Response ◽  
Biological Effects ◽  
Cell Types ◽  
P Glycoprotein ◽  
Colorectal Cancer Cells ◽  
The Status ◽  
Prevent Tumor Growth

Resveratrol has been proposed to prevent tumor growth and the different steps of carcinogenesis; nevertheless, these biological effects are sometimes discordant between different cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a different cellular response. We show here, using colorectal tumor cell lines, that the biological effects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these different transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells.

scholarly journals Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities

Cancers ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 207 ◽  
Author(s):  
Emily Rodrigues ◽  
Matthew Macauley
Keyword(s):  
Sialic Acid ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cell ◽  
Cell Types ◽  
Functional Roles ◽  
Cell Responses ◽  
Disease Prognosis ◽  
Sialic Acid Binding ◽  
Cancer Types

Cell surface glycosylation is dynamic and often changes in response to cellular differentiation under physiological or pathophysiological conditions. Altered glycosylation on cancers cells is gaining attention due its wide-spread occurrence across a variety of cancer types and recent studies that have documented functional roles for aberrant glycosylation in driving cancer progression at various stages. One change in glycosylation that can correlate with cancer stage and disease prognosis is hypersialylation. Increased levels of sialic acid are pervasive in cancer and a growing body of evidence demonstrates how hypersialylation is advantageous to cancer cells, particularly from the perspective of modulating immune cell responses. Sialic acid-binding receptors, such as Siglecs and Selectins, are well-positioned to be exploited by cancer hypersialylation. Evidence is also mounting that Siglecs modulate key immune cell types in the tumor microenvironment, particularly those responsible for maintaining the appropriate inflammatory environment. From these studies have come new and innovative ways to block the effects of hypersialylation by directly reducing sialic acid on cancer cells or blocking interactions between sialic acid and Siglecs or Selectins. Here we review recent works examining how cancer cells become hypersialylated, how hypersialylation benefits cancer cells and tumors, and proposed therapies to abrogate hypersialylation of cancer.

scholarly journals The Effect and Regulatory Mechanism of High Mobility Group Box-1 Protein on Immune Cells in Inflammatory Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1044
Author(s):  
Yun Ge ◽  
Man Huang ◽  
Yong-ming Yao
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
High Mobility ◽  
Cell Types ◽  
High Mobility Group ◽  
High Mobility Group Protein

High mobility group box-1 protein (HMGB1), a member of the high mobility group protein superfamily, is an abundant and ubiquitously expressed nuclear protein. Intracellular HMGB1 is released by immune and necrotic cells and secreted HMGB1 activates a range of immune cells, contributing to the excessive release of inflammatory cytokines and promoting processes such as cell migration and adhesion. Moreover, HMGB1 is a typical damage-associated molecular pattern molecule that participates in various inflammatory and immune responses. In these ways, it plays a critical role in the pathophysiology of inflammatory diseases. Herein, we review the effects of HMGB1 on various immune cell types and describe the molecular mechanisms by which it contributes to the development of inflammatory disorders. Finally, we address the therapeutic potential of targeting HMGB1.

scholarly journals Mini Review: Current Trends and Understanding of Exosome Therapeutic Potential in Corneal Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Anil Tiwari ◽  
Aastha Singh ◽  
Sudhir Verma ◽  
Sarah Stephenson ◽  
Tuhin Bhowmick ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Application ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Specific Therapy ◽  
Current Trends ◽  
Exosome Biogenesis ◽  
Purification Methods ◽  
Review Current

Exosomes are a subset of extracellular vesicles (EVs) that are secreted by most cell types. They are nanosized EVs ranging from 30 to 150 nm. The membrane-enclosed bodies originate by the process of endocytosis and mainly comprise DNA, RNA, protein, and lipids. Exosomes not only act as cell-to-cell communication signaling mediators but also have the potential to act as biomarkers for clinical application and as a promising carrier for drug delivery. Unfortunately, the purification methods for exosomes remain an obstacle. While most of the exosome researches are mainly focused on cancer, there are limited studies highlighting the importance of exosomes in ocular biology, specifically cornea-associated pathologies. Here, we summarize a brief description of exosome biogenesis, roles of exosomes and exosome-based therapies in corneal pathologies, and exosome bioengineering for tissue-specific therapy.

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