The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System

In vitrodifferentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimickingin vitrothese two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4+CD25+Foxp3+T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4+CD161+CD196+Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-βproduction. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

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Engineering nucleosomes for generating diverse chromatin assemblies

Nucleic Acids Research ◽

10.1093/nar/gkab070 ◽

2021 ◽

Author(s):

Zenita Adhireksan ◽

Deepti Sharma ◽

Phoi Leng Lee ◽

Qiuye Bao ◽

Sivaraman Padavattan ◽

...

Keyword(s):

Dynamic Properties ◽

Dna Nanostructures ◽

Macromolecular Assemblies ◽

Maximum Resolution ◽

Different Types ◽

Chromatin Structural ◽

Dna Fragment

Abstract Structural characterization of chromatin is challenging due to conformational and compositional heterogeneity in vivo and dynamic properties that limit achievable resolution in vitro. Although the maximum resolution for solving structures of large macromolecular assemblies by electron microscopy has recently undergone profound increases, X-ray crystallographic approaches may still offer advantages for certain systems. One such system is compact chromatin, wherein the crystalline state recapitulates the crowded molecular environment within the nucleus. Here we show that nucleosomal constructs with cohesive-ended DNA can be designed that assemble into different types of circular configurations or continuous fibers extending throughout crystals. We demonstrate the utility of the method for characterizing nucleosome compaction and linker histone binding at near-atomic resolution but also advance its application for tackling further problems in chromatin structural biology and for generating novel types of DNA nanostructures. We provide a library of cohesive-ended DNA fragment expression constructs and a strategy for engineering DNA-based nanomaterials with a seemingly vast potential variety of architectures and histone chemistries.

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B-1 cell: the precursor of a novel mononuclear phagocyte with immuno-regulatory properties

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652009000300013 ◽

2009 ◽

Vol 81 (3) ◽

pp. 489-496 ◽

Cited By ~ 11

Author(s):

José Daniel Lopes ◽

Mario Mariano

Keyword(s):

Mammalian Cells ◽

Giant Cells ◽

Mononuclear Phagocyte ◽

Different Types ◽

Series Of Experiments ◽

B1 Cells ◽

Regulatory Properties

Characterization of the origin, properties, functions and fate of cells is a fundamental task for the understanding of physiological and pathological phenomena. Despite the bulk of knowledge concerning the diverse characteristics of mammalian cells, some of them, such as B-1 cells, are still poorly understood. Here we report the results obtained in our laboratory on these cells in the last 10 years. After showing that B-1 cells could be cultured and amplified in vitro, a series of experiments were performed with these cells. They showed that B1 cells reside mostly in the peritoneal and pleural cavities, migrate to distant inflammatory foci, coalesce to form giant cells and participate in granuloma formation, both in vitro and in vivo. They are also able to present antigens to immunologically responsive cells and are endowed with regulatory properties. Further, we have also shown that these cells facilitate different types of infection as well as tumor growth and spreading. These data are presently reviewed pointing to a pivotal role that these cells may play in innate and acquired immunity.

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Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage

AJP Cell Physiology ◽

10.1152/ajpcell.00447.2008 ◽

2009 ◽

Vol 296 (1) ◽

pp. C124-C130 ◽

Cited By ~ 6

Author(s):

Takashi Kawasaki ◽

Mashkoor A. Choudhry ◽

Martin G. Schwacha ◽

Kirby I. Bland ◽

Irshad H. Chaudry

Keyword(s):

Dendritic Cell ◽

Antigen Presentation ◽

Ex Vivo ◽

Sham Operation ◽

Dc Functions ◽

Midline Laparotomy ◽

Shed Blood ◽

Cell Functions ◽

Splenic Dendritic Cell ◽

Ifn Γ

Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN mice (6–8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility class II expression, ability to produce cytokines, and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-α, IL-6, and IFN-γ from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-γ production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H.

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Antitumor and immunomodulatory activity of Inonotus obliquus

Herba Polonica ◽

10.1515/hepo-2017-0013 ◽

2017 ◽

Vol 63 (2) ◽

pp. 48-58 ◽

Cited By ~ 6

Author(s):

Justyna Staniszewska ◽

Marcin Szymański ◽

Ewa Ignatowicz

Keyword(s):

Immune System ◽

Tumor Cells ◽

Good Alternative ◽

Immunomodulatory Activity ◽

Host Immune System ◽

Protein Synthesis Inhibition ◽

Inonotus Obliquus ◽

Different Types

SummaryThe article presents the antitumor and immunomodulatory activity of compounds and extracts fromInonotus obliquus.Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention.In vitroexperiments have shown the inhibition of inflammation with the influence of action ofI. obliquusextracts; however,in vivoexperiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

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Design, Synthesis and Characterization of Some Novel benzamide derivatives and it's Pharmacological Screening

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst20723 ◽

2020 ◽

pp. 68-74 ◽

Cited By ~ 4

Author(s):

Akshay R. Yadav ◽

Shrinivas K. Mohite

Keyword(s):

Chemical Structure ◽

Design Synthesis ◽

Different Types ◽

Anti Inflammatory ◽

Benzoyl Isothiocyanate ◽

Pharmacological Screening ◽

Benzamide Derivatives

The new series of substituted N-(phenylcarbamothioyl)benzamide derivatives (2a-2f) was designed, development and synthesized by using conventional and microwave method. In present work 6 different N-(phenylcarbamothioyl)benzamide were synthesized. Substituted benzoyl chloride is converted into benzoyl isothiocyanate by esterification. Benzoyl isothiocyanate is converted into Substituted (phenylcarbamothioyl)benzamide by treating with different types of substituted aniline. Confirmation of the chemical structure of the synthesized was substantiated by TLC, IR, 1H NMR, MS spectroscopy.Novel synthesized compounds screened for their in vivo and in-vitro anti-inflammatory studies and compound 2f shows promising anti-inflammatory activity.

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Molecular cloning and characterization of a human metalloprotease disintegrin— a novel marker for dendritic cell differentiation

Blood ◽

10.1182/blood.v96.2.732.014k11_732_739 ◽

2000 ◽

Vol 96 (2) ◽

pp. 732-739 ◽

Cited By ~ 3

Author(s):

Jana Fritsche ◽

Markus Moser ◽

Stefan Faust ◽

Alice Peuker ◽

Reinhard Büttner ◽

...

Keyword(s):

Dendritic Cell ◽

Cell Lines ◽

Human Blood ◽

Messenger Rna ◽

Target Genes ◽

Monocytic Cell ◽

Dihydroxyvitamin D3 ◽

Dendritic Cell Differentiation

The 1,25-dihydroxyvitamin D3(1,25- [OH]2VD3) modulates the differentiation of monocytic cell lines and monocytes (MOs) in vitro. Up to now several target genes of 1,25(OH)2VD3have been described in monocytic cell lines; however, little is known about target genes in primary MOs. With the Differential Display technique, we found a transcript up-regulated by 1,25(OH)2VD3 in short-term cultured human blood MOs, which we called MADDAM (metalloprotease and disintegrin dendritic antigen marker; EMBL/GenBank/DDBJ accession no. Y13786). Northern blot analysis confirmed this result and revealed a signal of MADDAM messenger RNA (mRNA) at about 7.5 kilobases (kb). Long-term culture (more than 20 hours) of MOs during macrophage (MAC) differentiation led to a rapid and complete down-regulation of MADDAM expression. In contrast, MADDAM expression was maintained in MOs differentiated along the dendritic cell (DC) pathway and induced in CD34+-derived DCs. In addition, in situ hybridization revealed signals of MADDAM mRNA in follicles of human lymph nodes and MADDAM mRNA was detected in freshly isolated human blood-DCs by reverse transcription-polymerase chain reaction (RT-PCR). By means of a database search, we found that MADDAM is a member of the ADAM (a metalloprotease and disintegrin) family, the human homologue to murine meltrin-β (ADAM 19). From these data, we conclude that MADDAM is an important marker for the differentiation and characterization of DCs and the distinction between MACs and DCs.

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Staphylococcus aureusPhenol-Soluble Modulin Peptides Modulate Dendritic Cell Functions and Increase In Vitro Priming of Regulatory T Cells

The Journal of Immunology ◽

10.4049/jimmunol.1202563 ◽

2013 ◽

Vol 190 (7) ◽

pp. 3417-3426 ◽

Cited By ~ 43

Author(s):

Jens Schreiner ◽

Dorothee Kretschmer ◽

Juliane Klenk ◽

Michael Otto ◽

Hans-Jörg Bühring ◽

...

Keyword(s):

T Cells ◽

Dendritic Cell ◽

Regulatory T Cells ◽

Cell Functions

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Characterization of a humanized IgG4 anti-HLA-DR monoclonal antibody that lacks effector cell functions but retains direct antilymphoma activity and increases the potency of rituximab

Blood ◽

10.1182/blood-2006-04-017921 ◽

2006 ◽

Vol 108 (8) ◽

pp. 2736-2744 ◽

Cited By ~ 42

Author(s):

Rhona Stein ◽

Zhengxing Qu ◽

Susan Chen ◽

David Solis ◽

Hans J. Hansen ◽

...

Keyword(s):

Monoclonal Antibody ◽

Effector Cell ◽

Cell Functions ◽

Hla Dr ◽

Complement Dependent Cytotoxicity ◽

Survival Pathway ◽

Anti Cd20

AbstractHLA-DR is under investigation as a target for monoclonal antibody (mAb) therapy of malignancies. Here we describe a humanized IgG4 form of the anti-HLA-DR mAb L243, hL243γ4P (IMMU-114), generated to provide an agent with selectivity toward neoplastic cells that can kill without complement-dependent cytotoxicity (CDC) or antibody-dependent cellular-cytotoxicity (ADCC), so as to reduce reliance on intact immunologic systems in the patient and effector mechanism-related toxicity. In vitro studies show that replacing the Fc region of hL243γ1, a humanized IgG1 anti-HLA-DR mAb, with the IgG4 isotype abrogates the effector cell functions of the antibody (ADCC and CDC) while retaining its antigen-binding properties, antiproliferative capacity (in vitro and in vivo), and the ability to induce apoptosis concurrent with activation of the AKT survival pathway. Growth inhibition was evaluated compared with and in combination with the anti-CD20 mAb rituximab, with the combination being more effective than rituximab alone in inhibiting proliferation. Thus, hL243γ4P is indistinguishable from hL243γ1 and the parental murine mAb in assays dependent on antigen recognition. The abrogation of ADCC and CDC, which are believed to play a major role in side effects of mAb therapy, may make this antibody an attractive clinical agent. In addition, combination of hL243γ4P with rituximab offers the prospect for improved patient outcome.

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