scholarly journals Are interleukin-16 and thrombopoietin new tools for the in vitro generation of dendritic cells?

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4020-4028 ◽  
Author(s):  
Silvia Della Bella ◽  
Stefania Nicola ◽  
Inna Timofeeva ◽  
Maria Luisa Villa ◽  
Armando Santoro ◽  
...  
Keyword(s):  
T Cells ◽  
Surface Expression ◽  
Gm Csf ◽  
Human Cd34 ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α ◽  
Inhibitory Molecules ◽  
Tolerogenic Dcs

Abstract The effects of interleukin 16 (IL-16) on dendritic cell (DC) generation from human CD34+ progenitor cells are not known. Here, we show that IL-16 added to a basal cocktail comprised of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, Flt-3 ligand (Flt3L), and tumor necrosis factor α (TNF-α) does induce the CD34+ hematopoietic cells to proliferate in vitro and to differentiate into phenotypically and functionally mature DCs. IL-16 exerts this function more efficiently than stem cell factor (SCF) as a control, thrombopoietin (TPO), or IL-16 plus TPO. Moreover, we show that the combination of IL-16 plus TPO induces the generation of tolerogenic DCs, able to induce an anergic state in T cells that persists when T cells are rechallenged with immunogenic DCs. An altered pattern of cytokine production, a reduced expression of the C-type lectin DC-SIGN, and an increased surface expression of the inhibitory molecules immunoglobulin-like transcript 2 (ILT-2), ILT-3, and ILT-4 may all contribute to confer the tolerogenic properties of these DCs. Generation of tolerogenic DCs may aid the exploration of new therapeutic strategies to promote tolerance to autoantigens and prevent disease development. (Blood. 2004;104:4020-4028)

scholarly journals A Combination of Geniposide and Chlorogenic Acid Combination Ameliorates Nonalcoholic Steatohepatitis in Mice by Inhibiting Kupffer Cell Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xin Xin ◽  
Yue Jin ◽  
Xin Wang ◽  
Beiyu Cai ◽  
Ziming An ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Activation ◽  
Raw264.7 Cells ◽  
Chemical Components ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Underlying Mechanisms ◽  
Factor Α

The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. Activation of Kupffer cells (KCs) is central to the development of diet-induced NASH. We investigated whether a combination of two active chemical components, geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, and high-sugar drinking water, as well as RAW264.7 cells stimulated with lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the expression of cytokines secreted by hepatic macrophages, including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-α, inducible nitric oxide synthase (INOS), IL-1β, and IL-6 mRNA and TNF-α protein expression levels were suppressed upon GC treatment in RAW264.7 cells. Our findings suggest that GC has a strong anti-inflammatory effect in NASH, and this effect can be attributed to the suppression of KC activity in the liver.

scholarly journals Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zunera Zareen ◽  
Tammy Strickland ◽  
Victoria Mc Eneaney ◽  
Lynne A. Kelly ◽  
Denise McDonald ◽  
...  
Keyword(s):  
School Age Children ◽  
Therapeutic Window ◽  
School Age ◽  
Neonatal Encephalopathy ◽  
Gm Csf ◽  
Cytokine Responses ◽  
Tnf Α ◽  
Cytokine Dysregulation ◽  
Macrophage Colony

Abstract Background Cytokines are possible mediators of neuroinflammation and associated with adverse outcome in neonatal encephalopathy (NE). Our aim was to explore cytokine response in children with Neonatal Encephalopathy (NE) at school age compared to age-matched controls. Method Follow up at school age, children who had NE and age-matched controls were assessed for their cytokine responses and neurodevelopment outcome. Pro- and anti-inflammatory cytokines in the serum, [Interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, IL-18, Tumor necrosis factor (TNF)-α, TNF β, Interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), erythropoietin (EPO), IL-10 & IL-1RA] were measured at baseline and in response to in vitro stimulation with lipopolysaccharide (LPS: endotoxin). Results GM-CSF, TNF-β, IL-2 IL-6 and IL-8 were significantly elevated at school age following NE (n = 40) compared to controls (n = 37). A rise in GM-CSF, IL-8, TNF-α, IL-1β, & IL-6 were seen in NE group following LPS stimulation. Relative LPS hypo-responsiveness was also noted in children with severe NE with IL-10, VEGF, EPO and TNF-β. Elevated TNF-β was associated with low gross motor scores on assessment at school age. Conclusion School-age children post-NE had significantly altered cytokine responses to endotoxin compared to controls. TNF-β was associated with adverse developmental outcomes. This suggests the inflammatory process may persist into childhood and a longer therapeutic window may be available for neuroprotection therapies.

Leishmania donovani infection of bone marrow stromal macrophages selectively enhances myelopoiesis, by a mechanism involving GM-CSF and TNF-α

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1642-1651 ◽  
Author(s):  
Sara E. J. Cotterell ◽  
Christian R. Engwerda ◽  
Paul M. Kaye
Keyword(s):  
Infectious Disease ◽  
Bone Marrow ◽  
Stromal Cell ◽  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony

Alterations in hematopoiesis are common in experimental infectious disease. However, few studies have addressed the mechanisms underlying changes in hematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. In experimental visceral leishmaniasis, caused by infection with the protozoan parasite Leishmania donovani, parasites persist in the spleen and bone marrow, and their expansion in these sites is associated with increases in local hematopoietic activity. The results of this study show that L donovani targets bone marrow stromal macrophages in vivo and can infect and multiply in stromal cell lines of macrophage, but not other lineages in vitro. Infection of stromal macrophages increases their capacity to support myelopoiesis in vitro, an effect mediated mainly through the induction of granulocyte macrophage-colony stimulating factor and tumor necrosis factor-. These data are the first to directly demonstrate that intracellular parasitism of a stromal cell population may modify its capacity to regulate hematopoiesis during infectious disease.

scholarly journals Anti-lymphocyte globulin stimulates normal human T cells to proliferate and to release lymphokines in vitro. A study at the clonal level

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 956-963
Author(s):  
GC Barbano ◽  
A Schenone ◽  
S Roncella ◽  
R Ghio ◽  
A Corcione ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Suppressor Cells ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Recombinant Interleukin 2 ◽  
Macrophage Colony

Abstract Human peripheral blood mononuclear cells (PBMC) were stimulated in vitro with anti-lymphocyte globulin (ALG), and the phenotypic and functional properties of the blasts obtained were investigated. When stained with monoclonal antibodies (MoAbs), all of the blasts were identified as T cells that expressed predominantly the CD4 phenotype (70% of the cells). The remaining blasts were CD8+. These findings demonstrate that ALG stimulates both helper-inducer and cytotoxic- suppressor cells at random since the CD4 to CD8 ratio in the stimulated blasts was the same as in resting PBMC. This ratio is different from that observed in short-term cultures of T cells stimulated with phytohemagglutinin (PHA) under the same conditions (CD4 to CD8 ratio less than 1). ALG-stimulated T cells were cloned by limiting dilution in the presence of recombinant Interleukin-2 (rIL-2). The clones obtained were expanded and maintained in long term cultures with rIL-2. Thirty-two clones were tested for their capacity of producing colony stimulating activity (CSA) or burst promoting activity (BPA). Twenty- eight of them produced CSA and 12 produced BPA. No correlation was found between the surface phenotype and the ability of the clones to produce CSA or BPA (ie, both the CD4+ and CD8+ clones released the cytokines). When 16 of the same clones were tested for II-2 and gamma interferon (gamma IFN) production, 12 were found to be gamma INF and IL- 2 producers. All of the gamma IFN producers also released IL-2, whereas in the single clones no correlation was found with the capacity of releasing BPA and CSA. Supernatants from selected T-cell clones were also tested for hematopoietic growth factor activities in the presence of neutralizing antisera to human granulocyte-macrophage colony stimulating factor (GM-CSF) or to Interleukin-3 (IL-3). It was found that most CSA was attributable to GM-CSF, whereas BPA was mainly related to the presence of IL-3.

scholarly journals Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells.

1996 ◽  
Vol 133 (1) ◽  
pp. 159-167 ◽  
Author(s):  
A Saada ◽  
F Reichert ◽  
S Rotshenker
Keyword(s):  
Cell Surface ◽  
Schwann Cells ◽  
Interleukin 1 ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Gm Csf ◽  
Molecular Events ◽  
Macrophage Colony

Peripheral nerve injury is followed by Wallerian degeneration which is characterized by cellular and molecular events that turn the degenerating nerve into a tissue that supports nerve regeneration. One of these is the removal, by phagocytosis, of myelin that contains molecules which inhibit regeneration. We have recently documented that the scavenger macrophage and Schwann cells express the galactose-specific lectin MAC-2 which is significant to myelin phagocytosis. In the present study we provide evidence for a mechanism leading to the augmented expression of cell surface MAC-2. Nerve lesion causes noneuronal cells, primarily fibroblasts, to produce the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF). In turn, GM-CSF induces Schwann cells and macrophages to up-regulate surface expression of MAC-2. The proposed mechanism is based on the following novel observations. GM-CSF mRNA was detected by PCR in in vitro and in vivo degenerating nerves, but not in intact nerves. The GM-CSF molecule was detected by ELISA in medium conditioned by in vitro and in vivo degenerating peripheral nerves as of the 4th h after injury. GM-CSF activity was demonstrated by two independent bioassays, and repressed by activity blocking antibodies. Significant levels of GM-CSF were produced by nerve derived fibroblasts, but neither by Schwann cells nor by nerve derived macrophages. Mouse rGM-CSF enhanced MAC-2 production in nerve explants, and up-regulated cell surface expression of MAC-2 by Schwann cells and macrophages. Interleukin-1 beta up-regulated GM-CSF production thus suggesting that injury induced GM-CSF production may be mediated by interleukin-1 beta. Our findings highlight the fact that fibroblasts, by producing GM-CSF and thereby affecting macrophage and Schwann function, play a significant role in the cascade of molecular events and cellular interactions of Wallerian degeneration.

An Anti-c-Fms Antibody Inhibits Orthodontic Tooth Movement

2008 ◽  
Vol 87 (4) ◽  
pp. 396-400 ◽  
Author(s):  
H. Kitaura ◽  
M. Yoshimatsu ◽  
Y. Fujimura ◽  
T. Eguchi ◽  
H. Kohara ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Tooth Movement ◽  
Bone Erosion ◽  
Orthodontic Tooth Movement ◽  
Movement Model ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α

Orthodontic force induces osteoclastogenesis in vivo. It has recently been reported that administration of an antibody against the macrophage-colony-stimulating factor (M-CSF) receptor c-Fms blocks osteoclastogenesis and bone erosion induced by tumor necrosis factor-α (TNF-α) administration. This study aimed to examine the effect of an anti-c-Fms antibody on mechanical loading-induced osteoclastogenesis and osteolysis in an orthodontic tooth movement model in mice. Using TNF receptor 1- and 2-deficient mice, we showed that orthodontic tooth movement was mediated by TNF-α. We injected anti-c-Fms antibody daily into a local site, for 12 days, during mechanical loading. The anti-c-Fms antibody significantly inhibited orthodontic tooth movement, markedly reduced the number of osteoclasts in vivo, and inhibited TNF-α-induced osteoclastogenesis in vitro. These findings suggest that M-CSF plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption during orthodontic tooth movement mediated by TNF-α.

scholarly journals Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity

mBio ◽  
2010 ◽  
Vol 1 (4) ◽  
Author(s):  
Luisa Cervantes-Barragan ◽  
Roland Züst ◽  
Reinhard Maier ◽  
Sophie Sierro ◽  
Jozef Janda ◽  
...  
Keyword(s):  
T Cells ◽  
Specific Antigen ◽  
Antigen Delivery ◽  
Vaccine Vectors ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Human Coronavirus 229E

ABSTRACTEfficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cellsin vitroandin vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCsin vitroandin vivoresulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8+T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.IMPORTANCEVaccination against infectious agents has protected many individuals from severe disease. In addition, prophylactic and, most likely, also therapeutic vaccination against tumors will save millions from metastatic disease. This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cellsin vivo. Concomitant immunostimulation via the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was achieved through delivery by the same viral vector. Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8+T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. Moreover, highly efficient antigen delivery to human DCs with recombinant human coronavirus 229E and specific stimulation of human CD8+T cells revealed that this approach is exceptionally well suited for translation into human vaccine studies.

Arrest of human dendritic cells at the CD34−/CD4+/HLA-DR+ stage in the bone marrow of NOD/SCID-human chimeric mice

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3655-3657 ◽  
Author(s):  
Masaharu Nobuyoshi ◽  
Yoichiro Kusunoki ◽  
Toshio Seyama ◽  
Kazunori Kodama ◽  
Akiro Kimura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Chimeric Mice ◽  
Human Cord Blood ◽  
Gm Csf ◽  
Hla Dr ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α ◽  
Human Dendritic Cells

Human dendritic cell (DC) precursors were engrafted and maintained in NOD/SCID- human chimeric mice (NOD/SCID-hu mice) implanted with human cord blood mononuclear cells, although no mature human DCs were detected in lymphoid organs of the mice. Two months after implantation, bone marrow (BM) cells of NOD/SCID-hu mice formed colonies showing DC morphology and expressing CD1a in methylcellulose culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNF-α). The CD34−/CD4+/HLA-DR+ cell fraction in NOD/SCID-hu mouse BM generated CD1a+ cells that were highly stimulatory in mixed leukocyte reactions in culture with GM-CSF and TNF-α. These results suggest a strong potential for NOD/SCID-hu BM to generate human DCs, although DC differentiation may be blocked at the CD34−/CD4+/HLA-DR+ stage.

scholarly journals Extracellular purine metabolism and signaling of CD73-derived adenosine in murine Treg and Teff cells

2011 ◽  
Vol 301 (2) ◽  
pp. C530-C539 ◽  
Author(s):  
Michael Romio ◽  
Benjamin Reinbeck ◽  
Sabine Bongardt ◽  
Sandra Hüls ◽  
Sandra Burghoff ◽  
...  
Keyword(s):  
T Cells ◽  
Proinflammatory Cytokines ◽  
Wild Type ◽  
Murine Splenocytes ◽  
Gm Csf ◽  
A2a Receptors ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Ifn Γ ◽  
Macrophage Colony

CD73-derived adenosine acts as potent inhibitor of inflammation, and regulatory T cells (Treg) have been shown to express CD73 as a novel marker. This study explored the role of endogenously formed adenosine in modulating NF-κB activity and cytokine/chemokine release from murine Treg and effector T cells (Teff) including key enzymes/purinergic receptors of extracellular ATP catabolism. Stimulating murine splenocytes and CD4+ T cells with anti-CD3/anti-CD28 significantly upregulated activated NF-κB in CD73−/− T cells (wild type: 4.36 ± 0.21; CD73−/−: 6.58 ± 0.75; n = 4; P = 0.029). This was associated with an augmented release of proinflammatory cytokines IL-2, TNF-α, and IFN-γ. Similar changes were observed with the CD73 inhibitor APCP (50 μM) on NF-κB and IFN-γ in wild-type CD4+ T-cells. Treatment of stimulated CD4+ T-cells with adenosine (25 μM) potently reduced IFN-γ release which is mediated by adenosine A2a receptors (A2aR). AMP (50 μM) also reduced cytokine release which was not inhibited by APCP. In Teff, A2aR activation (CGS21680) potently inhibited the release of IL-1, IL-2, IL-3, IL-4, IL-12, IL-13, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), CCL3, and CCL4. However, in Treg, CGS21680 did not alter cytokine/chemokine release. In summary, CD73-derived adenosine tonically inhibits active NF-κB in CD4+ T-cells, thereby modulating the release of a broad spectrum of proinflammatory cytokines and chemokines. Downregulation of P2X7 and upregulation of CD73 in Treg after antigenic stimulation may be an important mechanism to maintain the ability of Treg to generate immunosuppressive adenosine.

scholarly journals The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 711-720 ◽  
Author(s):  
Mohammad Luqman ◽  
Sha Klabunde ◽  
Karen Lin ◽  
Georgios V. Georgakis ◽  
Anu Cherukuri ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Surface Expression ◽  
Lymphocytic Leukemia ◽  
The Novel ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Gm Csf ◽  
Tnf Α ◽  
Cd40 Activation ◽  
Induced Apoptosis

Abstract B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well as the receptor CD40. Activation of CD40 by its ligand (CD40L) induces proliferation and rescues the cells from spontaneous and chemotherapy-induced apoptosis. CD40 activation also induces secretion of cytokines, such as IL-6, IL-10, TNF-α, IL-8, and GM-CSF, which are involved in tumor cell survival, migration, and interaction with cells in the tumor microenvironment. Here we demonstrate that in primary B-CLL tumor cells, the novel antagonist anti-CD40 monoclonal antibody, HCD122, inhibits CD40L-induced activation of signaling pathways, proliferation and survival, and secretion of cytokines. Furthermore, HCD122 is also a potent mediator of antibody-dependent cellular cytotoxicity (ADCC), lysing B-CLL cells more efficiently than rituximab in vitro, despite a significantly higher number of cell surface CD20 binding sites compared with CD40. Unlike rituximab, however, HCD122 (formerly CHIR-12.12) does not internalize upon binding to the cells. Our data suggest that HCD122 may inhibit B-CLL growth by blocking CD40 signaling and by ADCC-mediated cell lysis.

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