CD38 as an immunomodulator in cancer

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

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HISTORIAN ON SOCIAL NETWORKS: SOME METHODOLOGICAL CONSIDERATIONS

10.47850/s.2020.1.63 ◽

2020 ◽

pp. 223-227

Author(s):

Vasily Syrov

Keyword(s):

Social Networks ◽

Decisive Role ◽

Professional Community ◽

Historical Knowledge ◽

Main Attention ◽

Web Technologies ◽

Research Findings ◽

Methodological Considerations ◽

And Function

The article discusses some of the research findings related to the topic of the place and function of histori-ans on social networks. The main attention is paid to identifying the role of web technologies in the con-ventional practices of creating historical knowledge creation of historical knowledge. It is emphasized that the thesis about blurring the boundaries between the professional community and users in general does not mean rejection of the recognition of the decisive role of the professional community in the production of knowledge. The ways and methods of historians' actions in social networks and their advantages over traditional methods of knowledge production are revealed.

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The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

Science Signaling ◽

10.1126/scisignal.aao4354 ◽

2018 ◽

Vol 11 (556) ◽

pp. eaao4354 ◽

Cited By ~ 1

Author(s):

Ivana Halova ◽

Monika Bambouskova ◽

Lubica Draberova ◽

Viktor Bugajev ◽

Petr Draber

Keyword(s):

Mast Cell ◽

Mast Cells ◽

T Cell Activation ◽

Cell Activation ◽

Adaptor Protein ◽

Prostaglandin E ◽

Dependent Manner ◽

And Function ◽

Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions

International Journal of Molecular Sciences ◽

10.3390/ijms21176118 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6118 ◽

Cited By ~ 1

Author(s):

Marianna Szczypka

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Splice Variants ◽

Cell Activity ◽

Cell Functions ◽

Simultaneous Inhibition ◽

And Function

Phosphodiesterase 7 (PDE7), a cAMP-specific PDE family, insensitive to rolipram, is present in many immune cells, including T lymphocytes. Two genes of PDE7 have been identified: PDE7A and PDE7B with three or four splice variants, respectively. Both PDE7A and PDE7B are expressed in T cells, and the predominant splice variant in these cells is PDE7A1. PDE7 is one of several PDE families that terminates biological functions of cAMP—a major regulating intracellular factor. However, the precise role of PDE7 in T cell activation and function is still ambiguous. Some authors reported its crucial role in T cell activation, while according to other studies PDE7 activity was not pivotal to T cells. Several studies showed that inhibition of PDE7 by its selective or dual PDE4/7 inhibitors suppresses T cell activity, and consequently T-mediated immune response. Taken together, it seems quite likely that simultaneous inhibition of PDE4 and PDE7 by dual PDE4/7 inhibitors or a combination of selective PDE4 and PDE7 remains the most interesting therapeutic target for the treatment of some immune-related disorders, such as autoimmune diseases, or selected respiratory diseases. An interesting direction of future studies could also be using a combination of selective PDE7 and PDE3 inhibitors.

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Progranulin attenuates liver fibrosis by downregulating the inflammatory response

Cell Death and Disease ◽

10.1038/s41419-019-1994-2 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 7

Author(s):

Wonbeak Yoo ◽

Jaemin Lee ◽

Kyung Hee Noh ◽

Sangmin Lee ◽

Dana Jung ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Cell Activation ◽

Stellate Cell ◽

Raw 264.7 Cells ◽

Protective Effects ◽

Deficient Diet ◽

A Cell

Abstract Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine‐choline‐deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.

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Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line

Blood ◽

10.1182/blood.v82.8.2537.2537 ◽

1993 ◽

Vol 82 (8) ◽

pp. 2537-2545 ◽

Cited By ~ 10

Author(s):

DD Hickstein ◽

E Grunvald ◽

G Shumaker ◽

DM Baker ◽

AL Back ◽

...

Keyword(s):

Cell Line ◽

Cell Activation ◽

Blast Crisis ◽

K562 Cells ◽

Myelogenous Leukemia ◽

Cell Clones ◽

A Cell ◽

Neutrophil Adherence ◽

The Individual

Abstract The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.

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MiR-146a in Immunity and Disease

Molecular Biology International ◽

10.4061/2011/437301 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 107

Author(s):

Nicole Rusca ◽

Silvia Monticelli

Keyword(s):

Immune Responses ◽

Recent Progress ◽

Viral Infections ◽

Cellular Functions ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Different Types ◽

A Cell ◽

And Function

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

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Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20112836 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2836 ◽

Cited By ~ 5

Author(s):

Grace Mallett ◽

Arian Laurence ◽

Shoba Amarnath

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Cell Surface Receptor ◽

Programmed Cell Death 1 ◽

Surface Receptor ◽

A Cell ◽

And Function

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.

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Evaluation of the Role of ABCB1gene Polymorphic Variants on Psychiatric Disorders Predisposition in Macedonian Population

PRILOZI ◽

10.2478/prilozi-2018-0008 ◽

2017 ◽

Vol 38 (3) ◽

pp. 71-88

Author(s):

Zorica Naumovska ◽

Aleksandra K. Nestorovska ◽

Zoran Sterjev ◽

Ana Filipce ◽

Aleksandra Grozdanova ◽

...

Keyword(s):

Bipolar Disorder ◽

Psychiatric Disorders ◽

Psychiatric Illness ◽

Cell Activation ◽

Bipolar Disorders ◽

Control Group ◽

Microglia Cell ◽

Increased Risk ◽

And Function

Abstract The psychiatric and other CNS disorders are characterized with unregulated neuro-inflammatory processes and chronic microglia cell activation resulting with detrimental effect. ABCB1gene polymorphismsC1236T, G2677T/Aand C3435T are associated with P-glycoprotein expression and function andare linked with predisposition to psychiatric disorders such as schizophrenia and bipolar disorders. The relationship between mood disorders and glucocorticoids has been confirmed and ABCB1 SNPs influence the glucocorticoids access to the brain. The aim of the study is evaluation of the influence of the three most common ABCB1SNPs on predisposition to psychiatric disorders in Macedonian population. In the study 107 unrelated healthy Macedonians of both sexes were enrolled as a control group and patient population of 54 patients (22 to 65 years old) diagnosed with schizophrenia or bipolar disorder. ABCB1 for three polymorphisms were analyzed by Real-Time PCR in both groups. The results have confirmed the role of the ABCB1 gene in predisposition to psychiatric disorders and increased risk of developing bipolar disorder in carriers of the heterozygotes and mutant homozygotes for polymorphic variations in 1236 and 2677 in comparison to the normal genotype carriers. Three-fold higher risk was estimated for psychiatric illness in women that are 1236 and 2677 heterozygous carrier (heterozygous and mutant homozygous) compared to healthy control (men and women) population and four-fold higher risk in comparison only to healthy women population. Mutant allele carriers for 1236 and 2677 polymorphisms that are 35 years and below in patients population have almost three-fold higher risk for development of psychiatric illness.

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CD38, a Receptor with Multifunctional Activities: From Modulatory Functions on Regulatory Cell Subsets and Extracellular Vesicles, to a Target for Therapeutic Strategies

Cells ◽

10.3390/cells8121527 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1527 ◽

Cited By ~ 3

Author(s):

Fabio Morandi ◽

Irma Airoldi ◽

Danilo Marimpietri ◽

Cristiano Bracci ◽

Angelo Corso Faini ◽

...

Keyword(s):

Cell Activation ◽

Plasma Cells ◽

Surface Protein ◽

Immune Defense ◽

Regulatory Cell ◽

Receptor Complexes ◽

Cd38 Expression ◽

Basic Criterion ◽

Cell Activation Marker ◽

A Cell

CD38 is a multifunctional cell surface protein endowed with receptor/enzymatic functions. The protein is generally expressed at low/intermediate levels on hematological tissues and some solid tumors, scoring the highest levels on plasma cells (PC) and PC-derived neoplasia. CD38 was originally described as a receptor expressed by activated cells, mainly T lymphocytes, wherein it also regulates cell adhesion and cooperates in signal transduction mediated by major receptor complexes. Furthermore, CD38 metabolizes extracellular NAD+, generating ADPR and cyclic ADPR. This ecto-enzyme controls extra-cellular nucleotide homeostasis and intra-cellular calcium fluxes, stressing its relevance in multiple physiopathological conditions (infection, tumorigenesis and aging). In clinics, CD38 was adopted as a cell activation marker and in the diagnostic/staging of leukemias. Quantitative surface CD38 expression by multiple myeloma (MM) cells was the basic criterion used for therapeutic application of anti-CD38 monoclonal antibodies (mAbs). Anti-CD38 mAbs-mediated PC depletion in autoimmunity and organ transplants is currently under investigation. This review analyzes different aspects of CD38’s role in regulatory cell populations and how these effects are obtained. Characterizing CD38 functional properties may widen the extension of therapeutic applications for anti-CD38 mAbs. The availability of therapeutic mAbs with different effects on CD38 enzymatic functions may be rapidly translated to immunotherapeutic strategies of cell immune defense.

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Early-life nutritional programming of longevity

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000294 ◽

2014 ◽

Vol 5 (5) ◽

pp. 325-338 ◽

Cited By ~ 32

Author(s):

A. M. Vaiserman

Keyword(s):

Early Life ◽

Epidemiological Studies ◽

Structure And Function ◽

Sufficient Evidence ◽

Scientific Publications ◽

Nutritional Programming ◽

Research Findings ◽

Regulation Mechanisms ◽

And Function

Available data from both experimental and epidemiological studies suggest that inadequate diet in early life can permanently change the structure and function of specific organs or homoeostatic pathways, thereby ‘programming’ the individual’s health status and longevity. Sufficient evidence has accumulated showing significant impact of epigenetic regulation mechanisms in nutritional programming phenomenon. The essential role of early-life diet in the development of aging-related chronic diseases is well established and described in many scientific publications. However, the programming effects on lifespan have not been extensively reviewed systematically. The aim of the review is to provide a summary of research findings and theoretical explanations that indicate that longevity can be influenced by early nutrition.

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