Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2191-2198 ◽  
Author(s):  
Roy Bheekha-Escura ◽  
Donald W. MacGlashan ◽  
Jacqueline M. Langdon ◽  
Susan M. MacDonald
Keyword(s):  
Histamine Release ◽  
Cell Line ◽  
Tnf Α ◽  
Eosinophilic Cell ◽  
Enhanced Secretion ◽  
High Affinity Receptor ◽  
Macrophage Colony ◽  
Cell Surface Structure ◽  
Factor Α ◽  
Induce Histamine Release

The human recombinant histamine-releasing factor (HrHRF) was previously shown to induce histamine release from human basophils from a subset of donors. The ability of HrHRF to directly induce histamine release from only certain basophils was thought to involve interaction between HrHRF and a particular kind of IgE, termed IgE+, on the surface of these cells. Recent studies disproved the hypothesis that the IgE molecule or its high-affinity receptor, FcεRI, is involved in secretion of histamine and cytokines by basophils stimulated with HrHRF. Rather, data suggest that HrHRF is a cytokine that stimulates basophils by binding to a cell-surface structure other than the IgE molecule. This report describes the effects of HrHRF on another inflammatory cell type: eosinophils from mildly allergic donors. In purified eosinophils primed with granulocyte-macrophage colony-stimulating factor, both tumor necrosis factor α (TNF-α) and HrHRF induced increased secretion of interleukin (IL) 8. In addition, both HrHRF and IL-5 enhanced secretion of IL-8 stimulated by TNF-α. Secretion of IL-8 reached a plateau level in less than 24 hours, was inhibited by cycloheximide, and required the presence of HrHRF throughout the culture period. In some eosinophil preparations, HrHRF induced calcium mobilization that was inhibited by pertussis toxin. Additionally, HrHRF caused secretion of IL-8 from the human eosinophilic cell line, AML14-3D10, which does not possess the α chain of FcεRI. These data provide evidence that HrHRF contributes to activation of eosinophils and thus suggest an additional role for HrHRF in the pathophysiologic mechanisms of allergic disease.

Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2191-2198 ◽  
Author(s):  
Roy Bheekha-Escura ◽  
Donald W. MacGlashan ◽  
Jacqueline M. Langdon ◽  
Susan M. MacDonald
Keyword(s):  
Histamine Release ◽  
Cell Line ◽  
Tnf Α ◽  
Eosinophilic Cell ◽  
Enhanced Secretion ◽  
High Affinity Receptor ◽  
Macrophage Colony ◽  
Cell Surface Structure ◽  
Factor Α ◽  
Induce Histamine Release

Abstract The human recombinant histamine-releasing factor (HrHRF) was previously shown to induce histamine release from human basophils from a subset of donors. The ability of HrHRF to directly induce histamine release from only certain basophils was thought to involve interaction between HrHRF and a particular kind of IgE, termed IgE+, on the surface of these cells. Recent studies disproved the hypothesis that the IgE molecule or its high-affinity receptor, FcεRI, is involved in secretion of histamine and cytokines by basophils stimulated with HrHRF. Rather, data suggest that HrHRF is a cytokine that stimulates basophils by binding to a cell-surface structure other than the IgE molecule. This report describes the effects of HrHRF on another inflammatory cell type: eosinophils from mildly allergic donors. In purified eosinophils primed with granulocyte-macrophage colony-stimulating factor, both tumor necrosis factor α (TNF-α) and HrHRF induced increased secretion of interleukin (IL) 8. In addition, both HrHRF and IL-5 enhanced secretion of IL-8 stimulated by TNF-α. Secretion of IL-8 reached a plateau level in less than 24 hours, was inhibited by cycloheximide, and required the presence of HrHRF throughout the culture period. In some eosinophil preparations, HrHRF induced calcium mobilization that was inhibited by pertussis toxin. Additionally, HrHRF caused secretion of IL-8 from the human eosinophilic cell line, AML14-3D10, which does not possess the α chain of FcεRI. These data provide evidence that HrHRF contributes to activation of eosinophils and thus suggest an additional role for HrHRF in the pathophysiologic mechanisms of allergic disease.

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 TNF-induced IL-8 and MCP-1 production in the eosinophilic cell line, EOL-1

1996 ◽  
Vol 5 (3) ◽  
pp. 218-223 ◽  
Author(s):  
L. A. Goldstein ◽  
R. M. Strieter ◽  
H. L. Evanoff ◽  
S. L. Kunkel ◽  
N. W. Lukacs
Keyword(s):  
Cell Line ◽  
Inflammatory Responses ◽  
Kinetic Studies ◽  
Inhibitory Effects ◽  
Chemokine Production ◽  
Eosinophil Cell ◽  
Tnf Α ◽  
Eosinophilic Cell ◽  
Suppressive Cytokine

The role of eosinophils in inflammation and their mode of activation is not well understood. Eosinophil accumulation and subsequent expression of cytokines at the site of inflammation may play a role in exacerbation of inflammatory responses. In the present study, we have examined the role of TNF-α in eosinophil activation and chemokine production using a human leukaemic eosinophil cell line, EOL-1. Initial studies demonstrated that TNF-α induced the upregulation of IL-8 and MCP-1 mRNA and protein. Kinetic studies indicated production of chemokines, IL-8 and MCP-1, as early as 4 h post-activation, with peak levels of chemokine produced at 8 h, and decreasing by 24 h post-TNF-α activation. When IL-10, a suppressive cytokine, was incubated with TNF-α and EOL-1 cells, no effect was observed on IL-8 and MCP-1 production. However, dexamethasone, a glucocorticoid, demonstrated potent inhibitory effects on the EOL-1-derived chemokines. These studies indicate that eosinophils may be a significant source of chemokines capable of participating in, and maintaining, leukocyte recruitment during inflammatory responses, such as asthma.

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.

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 Effects of porcine MyD88 knockdown on the expression of TLR4 pathway-related genes and proinflammatory cytokines

2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Chaohui Dai ◽  
Li Sun ◽  
Lihuai Yu ◽  
Guoqiang Zhu ◽  
Shenglong Wu ◽  
...  
Keyword(s):  
Cell Line ◽  
Proinflammatory Cytokines ◽  
Negative Control ◽  
Signalling Pathway ◽  
Mechanistic Study ◽  
Interferon Α ◽  
Toll Like Receptor ◽  
Pk15 Cell ◽  
Tnf Α ◽  
Factor Α

As a critical adapter protein in Toll-like receptor (TLR)/Interleukin (IL)-1R signalling pathway, myeloid differentiation protein 88 (MyD88) plays an important role in immune responses and host defence against pathogens. The present study was designed to provide a foundation and an important reagent for the mechanistic study of MyD88 and its role TLR/IL-1R signalling pathways in porcine immunity. Lentivirus-mediated RNAi was used to generate a porcine PK15 cell line with a silenced MyD88 gene and quantitative real-time PCR (qPCR) and Western blotting were used to detect changes in the expression of critical genes in the Toll-like receptor 4 (TLR4) signalling pathway. ELISA was used to measure the levels of seven proinflammatory cytokines–interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-6, IL-8, IL-12, macrophage inflammatory protein (MIP)-1α and MIP-1β–in cell culture supernatants after MyD88 silencing. We successfully obtained a PK15 cell line with 61% MyD88 mRNA transcript down-regulated. In PK15 cells with MyD88 silencing, the transcript levels of TLR4 and IL-1β were significantly reduced, whereas there were no significant changes in the expression levels of cluster of differentiation antigen 14 (CD14), interferon-α (IFN-α) or TNF-α. The ELISA results showed that the levels of most cytokines were not significantly changed apart from IL-8 without stimulation, which was significantly up-regulated. When cells were induced by lipopolysaccharide (LPS) (0.1 μg/ml) for 6 h, the global level of seven proinflammatory cytokines up-regulated and the level of IL-1β, TNF-α, IL-6, IL-8 and IL-12 of Blank and negative control (NC) group up-regulated more significantly than RNAi group (P<0.05), which revealed that the MyD88 silencing could reduce the TLR4 signal transduction which inhibited the release of proinflammatory cytokines and finally leaded to immunosuppression.

Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 736-742 ◽  
Author(s):  
Manfred Lehner ◽  
Thomas Felzmann ◽  
Katharina Clodi ◽  
Wolfgang Holter
Keyword(s):  
Cell Death ◽  
Lipoteichoic Acid ◽  
Type I Interferons ◽  
Interleukin 4 ◽  
Type I ◽  
Cell Recovery ◽  
Activation Induced Cell Death ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α

Abstract Both type I interferons (IFNs) as well as lipopolysaccharide (LPS) individually compromise selected monocytic or dendritic cell (DC) functions. This study investigates the influence of these agents on the differentiation and the regulation of cell death of monocyte-derived DCs generated in the presence of granulocyte-macrophage colony-stimulating factor plus interleukin-4 (IL-4). It is reported that excessive apoptosis occurred rapidly in monocyte-derived DC cultures, if IFN-α or IFN-β was added in combination with LPS or lipoteichoic acid (LTA). The small fraction of cells surviving in such cultures displayed a mature DC phenotype with expression of CD83, CD80, and CD86. IL-10 was found in the supernatants of monocyte-derived DC cultures, if supplemented with LPS or IFN-α plus LPS but not in control cultures. When monocyte-derived DCs were generated in the presence of IFN-α without LPS, these cells displayed an immature DC phenotype with a reduction of cell recovery but no overt apoptosis. However, the addition of LPS, LTA, LPS plus IFN-γ, or tumor necrosis factor α (TNF-α) plus prostaglandin E2 to such cells again resulted in the rapid induction of apoptosis in the majority of cells, together with a reduced production of IL-12 p70 and TNF-α. Together, these data indicate an exquisite sensitivity of monocyte-derived DCs to activation-induced cell death if generated in the presence of IFN-α, indicating the existence of an important mechanism of immunosuppression caused by IFN-α–inducing agents, such as viral or bacterial stimuli.

scholarly journals Isolation and Characterization of the Fungal Metabolite 3-O-Methylviridicatin as an Inhibitor of Tumour Necrosis Factor α-Induced Human Immunodeficiency Virus Replication

1998 ◽  
Vol 9 (2) ◽  
pp. 149-155 ◽  
Author(s):  
A Heguy ◽  
P Cai ◽  
P Meyn ◽  
D Houck ◽  
S Russo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Line ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Luciferase Reporter ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Α ◽  
Necrosis Factor

The cytokine tumour necrosis factor α (TNF-α) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-α-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-α induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR–luciferase reporter plasmid and a stable line was isolated in which TNF-α increased luciferase production by two- to threefold. This cell line was used to screen approximately 15 000 fungal extracts. An inhibitory activity specific for TNF-α-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-α activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 μM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-α, with an IC50 of 2.5 μM.

Differential regulation of granulocyte-macrophage colony-stimulating factor mRNA and protein expression in human thyrocytes and thyroid-derived fibroblasts by interleukin-1α and tumour necrosis factor-α

1996 ◽  
Vol 151 (2) ◽  
pp. 277-285 ◽  
Author(s):  
G Aust ◽  
A Hofmann ◽  
S Laue ◽  
S Ode-Hakim ◽  
W A Scherbaum
Keyword(s):  
Protein Expression ◽  
Tumour Necrosis Factor Α ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Interleukin 1Α ◽  
Macrophage Colony ◽  
Factor Α ◽  
Stimulating Factor ◽  
Necrosis Factor

Abstract In this study, we provide the first report on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human thyroid epithelial cells. Primary cultures of highly purified thyrocytes and thyroid-derived fibroblasts (n=3) and three thyroid anaplastic and one largely papillary carcinoma cell lines were exposed to different potent GM-CSF stimulators, employing interleukin 1α (Il-1α) and tumour necrosis factor-α (TNF-α). Cytokine mRNA levels were monitored by semiquantitative reverse transcriptase-PCR including an internal heterologous competitor fragment after 3, 6 and 18 h of culture. Culture supernatants were assayed for GM-CSF using a highly sensitive ELISA (detection limit ≤ 0·5 pg/ml) after 24 h. Basal GM-CSF mRNA expression was higher in fibroblasts and SW 1736 cells compared with thyrocytes, C 634, 8505 C and HTh 74 cells. GM-CSF was spontaneously secreted by fibroblasts (means ± s.e.m.; 43 ± 15 pg/ml), SW 1736 (59 ± 4 pg/ml), HTh 74 (34 ± 4 pg/ml) and C 643 cells (12 ± 1 pg/ml) but not by thyrocytes and 8505 C cells. Treatment with Il-1α (10 U/ml) resulted in a marked increase of GM-CSF mRNA within 3 h and an increase or induction of protein expression in thyrocyte (2350 ± 214 pg/ml), fibroblast (5242 ± 1400 pg/ml), SW 1736 (20016 ± 280 pg/ml) and C 643 cultures (1285 ± 79 pg/ml). Stimulation with TNF-α (10 U/ml) yielded divergent results. No significant increase of GM-CSF mRNA or protein expression was found in thyrocytes although TNF-α receptor expression in these cells is well documented. Stimulation with TNF-α resulted in an increased GM-CSF production in fibroblasts (361 ± 14 pg/ml), HTh 74 (148 ± 51 pg/ml) and SW 1736 cultures (235 ± 43 pg/ml). TSH (10 mU/ml) did not stimulate GM-CSF secretion in thyrocytes and HTh 74 cells, both expressing the TSH receptor. Phorbol 12-myristate 13-acetate (10 ng/ml) enhanced GM-CSF mRNA and protein levels in all cell types investigated. Our data suggest that both thyrocytes and fibroblasts synthesize GM-CSF in response to Il-1α, but only fibroblasts respond to TNF-α with a significant increase in GM-CSF. Anaplastic thyroid carcinomas are potential GM-CSF producers. Journal of Endocrinology (1996) 151, 277–285

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