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  1. Article: A személyre szabott medicina, a biomarker-kutatás és a gyógyszerfejlesztés új irányai.

    Németh, György / Jelinek, Ivett

    Magyar onkologia

    2013  Volume 57, Issue 1, Page(s) 5–10

    Abstract: In recent years, medicine has taken some important first steps toward a major paradigm shift that could result in a landslide for personalized therapies. Indeed, evidence-based medicine seems to yield to personalized medicine in multiple areas, including ...

    Title translation New directions in biomarker research, drug development and personalized medicine.
    Abstract In recent years, medicine has taken some important first steps toward a major paradigm shift that could result in a landslide for personalized therapies. Indeed, evidence-based medicine seems to yield to personalized medicine in multiple areas, including both the thinking patterns of healthcare workers and everyday medical practice. Nevertheless, although a steadily increasing number of personalized treatment modalities have recently become available for patients, so far, no breakthrough can be seen in the paradigm shift from evidence-based medicine to personalized therapy. We believe that a more efficient identification and utilisation of future and already known biomarkers, respectively, might be the key to speed up this progress. In line with this, biomarkers are becoming increasingly important tools in late stage research, drug development and in clinical practice, as well. Correct classification of biomarkers becomes especially important, as different types of biomarkers provide markedly different information to drug developers and health care professionals.
    MeSH term(s) Biomarkers ; Biomarkers, Tumor ; Chronic Disease/drug therapy ; Drug Design ; Evidence-Based Medicine ; Humans ; Molecular Targeted Therapy/trends ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Pathology, Molecular ; Pharmacogenetics ; Precision Medicine/trends ; Predictive Value of Tests ; Prognosis ; Reagent Kits, Diagnostic
    Chemical Substances Biomarkers ; Biomarkers, Tumor ; Reagent Kits, Diagnostic
    Language Hungarian
    Publishing date 2013-03
    Publishing country Hungary
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 414033-3
    ISSN 0025-0244
    ISSN 0025-0244
    DOI MagyOnkol.2013.57.1.5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2.

    Simon, Tünde / Gogolák, Péter / Kis-Tóth, Katalin / Jelinek, Ivett / László, Valéria / Rajnavölgyi, Eva

    International immunology

    2012  Volume 24, Issue 2, Page(s) 107–116

    Abstract: Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. ... ...

    Abstract Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a(-) and CD1a(+) monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific manner. Histamine shifts DC differentiation to the development of CD1a(-) DCs and modulates DC activation through its inhibitory effect on CD1a(+) DC differentiation. Histamine-induced reduction of CD1a(+) DCs is associated with increased secretion of IL-6 and IL-10, up-regulation of a typical combination of chemokines, expression C5aR1 by the CD1a(-) DC subset and enhanced migration of both activated DC subsets supported by the production of MMP-9 and MMP-12 enzymes. All these effects were shown to be mediated in a H2R-specific manner as revealed by the specific antagonist of the receptor. As H2R is expressed at high levels in both DC subsets, we propose that it may dominate the regulation of multiple DC functions. In contrast, H1R and H4R with opposing subset-related expression may have a regulatory or fine-tuning role in histamine-induced functional activities.
    MeSH term(s) Antigens, CD1/genetics ; Antigens, CD1/immunology ; Antigens, CD1/metabolism ; Biomarkers/metabolism ; Cell Differentiation/drug effects ; Cell Lineage ; Cell Movement/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Gene Expression Regulation/drug effects ; Histamine/immunology ; Histamine/pharmacology ; Humans ; Immunomodulation ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 9/metabolism ; Monocytes/drug effects ; Monocytes/immunology ; Receptor, Anaphylatoxin C5a ; Receptors, Complement/genetics ; Receptors, Complement/metabolism ; Receptors, Histamine/genetics ; Receptors, Histamine/metabolism
    Chemical Substances Antigens, CD1 ; Biomarkers ; C5AR1 protein, human ; CD1a antigen ; Interleukin-6 ; Receptor, Anaphylatoxin C5a ; Receptors, Complement ; Receptors, Histamine ; Interleukin-10 (130068-27-8) ; Histamine (820484N8I3) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2012-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxr107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC⁻/⁻) mice

    Horváth, Zsuzsanna / Pállinger, Éva / Horváth, Győző / Jelinek, Ivett / Veszely, Gizella / Fűrész, József / Falus, András / Buzás, Edit I

    Inflammation research. 2010 June, v. 59, no. 6

    2010  

    Abstract: Objective and design In this study we investigated the role of histamine on the extramedullary hematopoiesis. Methods Male histidine decarboxylase knockout (HDC⁻/⁻) mice and wild-type mice were used (n = 5/group). Groups of mice received sublethal total- ... ...

    Abstract Objective and design In this study we investigated the role of histamine on the extramedullary hematopoiesis. Methods Male histidine decarboxylase knockout (HDC⁻/⁻) mice and wild-type mice were used (n = 5/group). Groups of mice received sublethal total-body gamma irradiation at a single dose of 4 Gy. Spleen cells were studied at different time points post-irradiation by flow cytometry, colony forming unit (CFU) assay, and real-time PCR. For statistical analysis Student's t test, ANOVA, and Holm-Sidak post-hoc test were used. Results By day 14 after irradiation, spleen cell counts increased almost eightfold in wild-type and not even fourfold in HDC⁻/⁻ mice (P < 0.01). The proliferative capacity and interleukin-3 signaling of stem cells were impaired in HDC⁻/⁻ mice. STAT5 mRNA expression was decreased in granulocyte-myeloid colonies by 72.9 ± 8.6% (P < 0.001), compared to the wild-type. Conclusions The absence of histamine adversely affects splenic hematopoiesis via direct and indirect mechanisms.
    Keywords spleen ; histamine ; hematopoiesis
    Language English
    Dates of publication 2010-06
    Size p. 429-436.
    Publisher SP Birkhäuser Verlag Basel
    Publishing place Basel
    Document type Article
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-009-0114-7
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Increased antigen presentation and T(h)1 polarization in genetically histamine-free mice.

    Jelinek, Ivett / László, Valéria / Buzás, Edit / Pállinger, Eva / Hangya, Balázs / Horváth, Zsuzsanna / Falus, András

    International immunology

    2007  Volume 19, Issue 1, Page(s) 51–58

    Abstract: Histamine is a well-known inflammatory mediator exerting various immunomodulatory effects and affecting the development of antigen-specific immune responses. Dendritic cells (DCs) are the most potent antigen-presenting cells specialized for capture, ... ...

    Abstract Histamine is a well-known inflammatory mediator exerting various immunomodulatory effects and affecting the development of antigen-specific immune responses. Dendritic cells (DCs) are the most potent antigen-presenting cells specialized for capture, uptake, transport, processing and presentation of antigens to T cells. Using a genetically histamine-free [histidine decarboxylase knockout (HDC-/-)] mouse model, we examined the effects of histamine on DC-mediated antigen presentation. Applying an in vitro antigen presentation assay, we found that spleen DCs, derived from HDC-/- mice, display a higher efficiency in antigen presentation compared with wild-type cells. Flow cytometric characterization of DCs disclosed that this difference was not due to an altered distribution of DCs between or within the major functional sub-populations (assessed by CD11b and CD4 as myeloid and CD8alpha and DEC205 as lymphoid DC markers) or major changes in the co-stimulatory molecule profile (CD40, CD80, CD86). However, real-time PCR analysis of in vivo CFA-induced IL-12p35, IFNgamma, IL-10 and IL-4 expression showed that DCs matured in a histamine-free environment exhibit significantly elevated levels of IL-12p35 and IFNgamma mRNA. In vitro investigations confirmed that isolated DCs, developed in the absence of histamine, exhibit indeed a predominantly T(h)1-polarized cytokine pattern, as they show elevated levels of IFNgamma mRNA upon LPS stimulation. Similar difference was found at the protein level by ELISA, as well. Our study demonstrates that histamine interferes with antigen presentation and alters the cytokine profile of DCs.
    MeSH term(s) Animals ; Antigen Presentation/immunology ; Antigens, CD/metabolism ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Flow Cytometry ; Histamine/physiology ; Histidine Decarboxylase/genetics ; Interferon-gamma/genetics ; Interleukin-12 Subunit p35/genetics ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Polymerase Chain Reaction ; RNA, Messenger/metabolism ; Spleen/cytology ; Th1 Cells/immunology
    Chemical Substances Antigens, CD ; Cytokines ; Interleukin-12 Subunit p35 ; Lipopolysaccharides ; RNA, Messenger ; Histamine (820484N8I3) ; Interferon-gamma (82115-62-6) ; Histidine Decarboxylase (EC 4.1.1.22)
    Language English
    Publishing date 2007-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxl121
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  5. Article: Carbohydrate recognition systems in autoimmunity.

    Buzás, Edit I / György, Bence / Pásztói, Mária / Jelinek, Ivett / Falus, András / Gabius, Hans-Joachim

    Autoimmunity

    2006  Volume 39, Issue 8, Page(s) 691–704

    Abstract: The immune system is a complex functional network of diverse cells and soluble molecules orchestrating innate and adaptive immunity. Biological information, to run these intricate interactions, is not only stored in protein sequences but also in the ... ...

    Abstract The immune system is a complex functional network of diverse cells and soluble molecules orchestrating innate and adaptive immunity. Biological information, to run these intricate interactions, is not only stored in protein sequences but also in the structure of the glycan part of the glycoconjugates. The spatially accessible carbohydrate structures that contribute to the cell's glycome are decoded by versatile recognition systems in order to maintain the immune homeostasis of an organism. Microbial carbohydrate structures are recognized by pathogen associated molecular pattern (PAMP) receptors of innate immunity including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT cells. Natural autoantibodies, a long known effector branch of this network-based operation, are effective to home in on non-self and self-glycosylation also. The recirculating pool of mammalian immune cells is recruited to inflammatory sites by a reaction pathway involving the self-carbohydrate-binding selectins as initial recognition step. Galectins, further key sensors reading the high-density sugar code, exert regulatory functions on activated T cells, among other activities. Autoimmune diseases are being associated with defined changes of glycosylation. This correlation deserves to be thoroughly studied on the levels of structural mimicry and dysregulation as well as effector molecules to devise innovative anti-inflammatory strategies. This review briefly summarizes data on sensor systems for carbohydrate epitopes and implications for autoimmunity.
    MeSH term(s) Animals ; Autoimmunity ; Carbohydrates/chemistry ; Carbohydrates/immunology ; Epitopes/chemistry ; Epitopes/immunology ; Humans ; Signal Transduction/immunology ; Systems Biology
    Chemical Substances Carbohydrates ; Epitopes
    Language English
    Publishing date 2006-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1025450-x
    ISSN 0891-6934
    ISSN 0891-6934
    DOI 10.1080/08916930601061470
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  6. Article: Histamine H1 and H2 receptors but not H4 receptors are upregulated during bone marrow regeneration.

    Horváth, Zsuzsanna / Pállinger, Eva / Horváth, Gyozo / Jelinek, Ivett / Falus, András / Buzás, Edit I

    Cellular immunology

    2006  Volume 244, Issue 2, Page(s) 110–115

    Abstract: The role of histamine receptors in radiation-induced bone marrow (BM) regeneration was investigated with aspects of functional genomics. H1R and H2R mRNA expression increased during regeneration in both histidine decarboxylase knockout (HDC-/-) and wild ... ...

    Abstract The role of histamine receptors in radiation-induced bone marrow (BM) regeneration was investigated with aspects of functional genomics. H1R and H2R mRNA expression increased during regeneration in both histidine decarboxylase knockout (HDC-/-) and wild type (HDC+/+) mice, though to a lesser extent in HDC-/- mice. H4R mRNA expression was downregulated in both groups. Mainly CD34+ cells were responsible for the elevation of intracellular histamine and HDC content in HDC+/+ BM cell populations. The differential changes in the expression of its receptors, and also its elevated levels in hematopoietic progenitors support the regulatory role of histamine in BM regeneration, that could be further explored by future gene expression studies.
    MeSH term(s) Animals ; Bone Marrow/physiology ; Flow Cytometry ; Hematopoiesis/physiology ; Histidine Decarboxylase/biosynthesis ; Histidine Decarboxylase/genetics ; Histidine Decarboxylase/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Receptors, G-Protein-Coupled/biosynthesis ; Receptors, G-Protein-Coupled/genetics ; Receptors, Histamine/biosynthesis ; Receptors, Histamine/genetics ; Receptors, Histamine H1/biosynthesis ; Receptors, Histamine H1/genetics ; Receptors, Histamine H2/biosynthesis ; Receptors, Histamine H2/genetics ; Receptors, Histamine H4 ; Regeneration/genetics ; Regeneration/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation
    Chemical Substances Hrh4 protein, mouse ; RNA, Messenger ; Receptors, G-Protein-Coupled ; Receptors, Histamine ; Receptors, Histamine H1 ; Receptors, Histamine H2 ; Receptors, Histamine H4 ; Histidine Decarboxylase (EC 4.1.1.22)
    Language English
    Publishing date 2006-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2007.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC-/-) mice.

    Horváth, Zsuzsanna / Pállinger, Eva / Horváth, Gyozo / Jelinek, Ivett / Veszely, Gizella / Furész, József / Falus, András / Buzás, Edit I

    Inflammation research : official journal of the European Histamine Research Society ... [et al.

    2009  Volume 59, Issue 6, Page(s) 429–436

    Abstract: Objective and design: In this study we investigated the role of histamine on the extramedullary hematopoiesis.: Methods: Male histidine decarboxylase knockout (HDC(-/-)) mice and wild-type mice were used (n = 5/group). Groups of mice received ... ...

    Abstract Objective and design: In this study we investigated the role of histamine on the extramedullary hematopoiesis.
    Methods: Male histidine decarboxylase knockout (HDC(-/-)) mice and wild-type mice were used (n = 5/group). Groups of mice received sublethal total-body gamma irradiation at a single dose of 4 Gy. Spleen cells were studied at different time points post-irradiation by flow cytometry, colony forming unit (CFU) assay, and real-time PCR. For statistical analysis Student's t test, ANOVA, and Holm-Sidak post-hoc test were used.
    Results: By day 14 after irradiation, spleen cell counts increased almost eightfold in wild-type and not even fourfold in HDC(-/-) mice (P < 0.01). The proliferative capacity and interleukin-3 signaling of stem cells were impaired in HDC(-/-) mice. STAT5 mRNA expression was decreased in granulocyte-myeloid colonies by 72.9 +/- 8.6% (P < 0.001), compared to the wild-type.
    Conclusions: The absence of histamine adversely affects splenic hematopoiesis via direct and indirect mechanisms.
    MeSH term(s) Animals ; Cell Cycle/drug effects ; Cells, Cultured ; Colony-Forming Units Assay ; Flow Cytometry ; Hematopoiesis, Extramedullary/genetics ; Hematopoiesis, Extramedullary/physiology ; Histamine/physiology ; Histidine Decarboxylase/genetics ; Histidine Decarboxylase/physiology ; Interleukin-3/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Regeneration ; Reverse Transcriptase Polymerase Chain Reaction ; STAT5 Transcription Factor/biosynthesis ; STAT5 Transcription Factor/genetics ; Spleen/cytology ; Spleen/drug effects ; Stem Cells/drug effects ; Whole-Body Irradiation
    Chemical Substances Interleukin-3 ; RNA, Messenger ; STAT5 Transcription Factor ; Histamine (820484N8I3) ; Histidine Decarboxylase (EC 4.1.1.22)
    Language English
    Publishing date 2009-11-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1221794-3
    ISSN 1420-908X ; 1023-3830
    ISSN (online) 1420-908X
    ISSN 1023-3830
    DOI 10.1007/s00011-009-0114-7
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  8. Article: Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.

    Kiss, Róbert / Kiss, Béla / Könczöl, Arpád / Szalai, Ferenc / Jelinek, Ivett / László, Valéria / Noszál, Béla / Falus, András / Keseru, György M

    Journal of medicinal chemistry

    2008  Volume 51, Issue 11, Page(s) 3145–3153

    Abstract: A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R ... ...

    Abstract A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were tested by radioligand binding assay and 16 of them possessed significant [(3)H]histamine displacement. Several novel scaffolds were identified that can be used to develop selective H4 ligands in the future. As far as we know, this is the first SBVS reported on H4R, representing one of the largest virtual screens validated by the biological evaluation of the virtual hits.
    MeSH term(s) Binding, Competitive ; Cell Line, Tumor ; Databases, Factual ; Histamine Antagonists/chemistry ; Histamine Antagonists/pharmacology ; Humans ; Ligands ; Models, Molecular ; Radioligand Assay ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Histamine/chemistry ; Receptors, Histamine/metabolism ; Receptors, Histamine H4 ; Structure-Activity Relationship
    Chemical Substances HRH4 protein, human ; Histamine Antagonists ; Ligands ; Receptors, G-Protein-Coupled ; Receptors, Histamine ; Receptors, Histamine H4
    Language English
    Publishing date 2008-06-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm7014777
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  9. Article ; Online: TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection.

    Jelinek, Ivett / Leonard, Joshua N / Price, Graeme E / Brown, Kevin N / Meyer-Manlapat, Anna / Goldsmith, Paul K / Wang, Yan / Venzon, David / Epstein, Suzanne L / Segal, David M

    Journal of immunology (Baltimore, Md. : 1950)

    2011  Volume 186, Issue 4, Page(s) 2422–2429

    Abstract: Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA ...

    Abstract Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA required to activate DC and the expression patterns of TLR3 protein in DC subsets have not been established. In this article, we show that cross-priming CD8α(+) and CD103(+) DC subsets express much greater levels of TLR3 than other DC. In resting DC, TLR3 is located in early endosomes and other intracellular compartments but migrates to LAMP1(+) endosomes on stimulation with a TLR3 ligand. Using homogeneous dsRNA oligonucleotides (ONs) ranging in length from 25 to 540 bp, we observed that a minimum length of ∼90 bp was sufficient to induce CD86, IL-12p40, IFN-β, TNF-α, and IL-6 expression, and to mature DC into APC that cross-presented exogenous Ags to CD8(+) T cells. TLR3 was essential for activation of DC by dsRNA ONs, and the potency of activation increased with dsRNA length and varied between DC subsets. In vivo, dsRNA ONs, in a size-dependent manner, served as adjuvants for the generation of Ag-specific CTL and for inducing protection against lethal challenge with influenza virus when given with influenza nucleoprotein as an immunogen. These results provide the basis for the development of TLR3-specific adjuvants capable of inducing immune responses tailored for viral pathogens.
    MeSH term(s) Adaptive Immunity/genetics ; Adjuvants, Immunologic/therapeutic use ; Animals ; Cells, Cultured ; CpG Islands/immunology ; Cross-Priming/immunology ; Cytotoxicity Tests, Immunologic ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/virology ; Epitopes, T-Lymphocyte/biosynthesis ; Epitopes, T-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/therapeutic use ; Female ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Oligodeoxyribonucleotides/therapeutic use ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/metabolism ; Orthomyxoviridae Infections/prevention & control ; RNA, Double-Stranded/therapeutic use ; Signal Transduction/genetics ; Signal Transduction/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/virology ; Toll-Like Receptor 3/deficiency ; Toll-Like Receptor 3/immunology ; Toll-Like Receptor 3/therapeutic use
    Chemical Substances Adjuvants, Immunologic ; CPG-oligonucleotide ; Epitopes, T-Lymphocyte ; Influenza Vaccines ; Oligodeoxyribonucleotides ; RNA, Double-Stranded ; TLR3 protein, mouse ; Toll-Like Receptor 3
    Language English
    Publishing date 2011-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1002845
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma.

    Nemeth, Krisztian / Keane-Myers, Andrea / Brown, Jared M / Metcalfe, Dean D / Gorham, James D / Gorham, Jared D / Bundoc, Virgilio G / Bundoc, Victor G / Hodges, Marcus G / Jelinek, Ivett / Madala, Satish / Karpati, Sarolta / Mezey, Eva

    Proceedings of the National Academy of Sciences of the United States of America

    2010  Volume 107, Issue 12, Page(s) 5652–5657

    Abstract: Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC- ... ...

    Abstract Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-beta production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions--specifically therapy resistant asthma--might also be a likely target of the recently discovered cellular therapy approach using BMSCs.
    MeSH term(s) Ambrosia/adverse effects ; Ambrosia/immunology ; Animals ; Asthma/etiology ; Asthma/immunology ; Asthma/pathology ; Asthma/therapy ; Bronchoalveolar Lavage Fluid/cytology ; Bronchoalveolar Lavage Fluid/immunology ; Cytokines/deficiency ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Humans ; Immunosuppression ; In Vitro Techniques ; Lung/immunology ; Lung/pathology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Th2 Cells/immunology ; Transforming Growth Factor beta/immunology ; Transplantation, Homologous ; Transplantation, Isogeneic
    Chemical Substances Cytokines ; Transforming Growth Factor beta
    Language English
    Publishing date 2010-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0910720107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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