IL-10–producing macrophages preferentially clear early apoptotic cells

Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4930-4937 ◽  
Author(s):  
Wei Xu ◽  
Anja Roos ◽  
Nicole Schlagwein ◽  
Andrea M. Woltman ◽  
Mohamed R. Daha ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Apoptotic Cells ◽  
Gm Csf ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Anti Inflammatory ◽  
Macrophage Colony ◽  
Macrophage Subset ◽  
Factor Α

AbstractEfficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)–driven macrophages (Mø2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This macrophage subset has intrinsic anti-inflammatory properties, characterized by high interleukin-10 (IL-10) production in the absence of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-α (TNF-α). Importantly, whereas the IL-6 and TNF-α production by granulocyte-macrophage (GM)–CSF–driven macrophages (Mø1s) is inhibited upon uptake of apoptotic cells, the anti-inflammatory status of Mø2 is retained during phagocytosis. Mø2s were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells. Mø2s showed more potent macropinocytosis compared with dendritic cells (DCs) and Mø1s, and uptake of apoptotic cells was inhibited by a macropinocytosis inhibitor. Our studies suggest that, under steady-state conditions, IL-10–producing Mø2s are prominently involved in the clearance of early apoptotic cells.

scholarly journals Anti-Inflammatory Effects of Phlebia sp. Extract in Lipopolysaccharide-stimulated RAW 264.7 Macrophages

2021 ◽  
Author(s):  
Eui Hyeon Lim ◽  
Seul-Ki Mun ◽  
Jong-Jin Kim ◽  
Dong-Jo Chang ◽  
Sung-Tae Yee
Keyword(s):  
Tissue Damage ◽  
Biological Activities ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Anti Inflammatory ◽  
Macrophage Colony ◽  
Factor Α

Lichens are a life form in which algae and fungi have a symbiotic relationship. A lichen has various biological activities, including anti-inflammatory and anti-proliferative activities. Inflammation is a response caused by various factors, such as infection by pathogens or tissue damage; excessive reactions can contribute to the etiology of chronic diseases, such as asthma, brain damage, and serious tissue damage. This study demonstrates the anti-inflammatory effect of ethyl acetate extract from Phlebia sp. on NF-κB and AP-1 pathways in the lipopolysaccharide-treated RAW 264.7 cell. Especially, Phlebia sp. extract inhibits the phosphorylation of AP-1 signaling (c-Fos and c-Jun) and its upstream MKK/MAPKs (MKK4, MKK7 and JNK), which induced a decrease in the production of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in downstream of AP-1 signaling. Furthermore, Phlebia sp. extract inhibited the production of final inflammatory effector molecules involved in AP-1 signaling, including nitric oxide (NO) and prostaglandin E2 (PGE2). Here, we report that Phlebia sp. extract has the potential to be developed as an anti-inflammatory agent.

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

scholarly journals Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Tomohiro Koga ◽  
Kaori Furukawa ◽  
Kiyoshi Migita ◽  
Shimpei Morimoto ◽  
Toshimasa Shimizu ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gm Csf ◽  
Tnf Α ◽  
Mediterranean Fever ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Factor Α ◽  
Stimulating Factor ◽  
Necrosis Factor

Abstract Objective To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis. Method We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis. Results Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%). Conclusion Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines.

scholarly journals Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice Have Impaired Resistance to Blood-Stage Malaria

2001 ◽  
Vol 69 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Julie Riopel ◽  
MiFong Tam ◽  
Karkada Mohan ◽  
Michael W. Marino ◽  
Mary M. Stevenson
Keyword(s):  
Blood Stage ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Blood Stage Malaria

ABSTRACT The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudiAS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice. Serum levels of gamma interferon (IFN-γ) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-γ levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-α) levels were significantly increased in KO mice and were significantly higher than TNF-α levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-γ and TNF-α production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.

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 Antitumour and Anti-Inflammatory Effects of Palladium(II) Complexes on Ehrlich Tumour

2013 ◽  
Vol 68 (7-8) ◽  
pp. 293-301
Author(s):  
Marcela B. Quilles ◽  
Camila B. A. Carli ◽  
Sandra R. Ananias ◽  
Lucas S. Ferreira ◽  
Livia C. A. Ribeiro ◽  
...  
Keyword(s):  
Mutagenic Activity ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
Tnf Α ◽  
Ehrlich Ascites Tumour ◽  
Eat Cells ◽  
Anti Inflammatory ◽  
Diphenyl Tetrazolium Bromide ◽  
Factor Α

Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-α (TNF-α), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 ± 3.23) μM and (137.65 ± 0.22) μM for 1 and (39.7 ± 0.30) μM and (146.51 ± 2.67) μM for 2, respectively. The production of NO, IL-12, and TNF-α, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin

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.

Extracellular signal-regulated kinase mediates granulocyte-macrophage colony-stimulating factor messenger RNA stabilization in tumor necrosis factor-α plus fibronectin-activated peripheral blood eosinophils

Blood ◽  
2002 ◽  
Vol 99 (11) ◽  
pp. 4048-4052 ◽  
Author(s):  
Stéphane Esnault ◽  
James S. Malter
Keyword(s):  
Messenger Rna ◽  
Mrna Stabilization ◽  
Extracellular Signal Regulated Kinase ◽  
Gm Csf ◽  
Extracellular Signal ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Factor Α ◽  
Blood Eosinophils ◽  
Necrosis Factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is critical for promoting the long-term survival of lung- or airway-based eosinophils. Previously, we have shown that fibronectin and tumor necrosis factor α induced autocrine production of GM-CSF that markedly enhanced eosinophil survival. Cytokine release was preceded by and dependent on messenger RNA (mRNA) stabilization. Here, we show that mitogen-activated protein kinase (MAPK) activation is responsible for GM-CSF mRNA stabilization in peripheral blood eosinophils (pbeos). Activation of extracellular signal-regulated kinase (ERK) but not p38 correlated with GM-CSF mRNA stability. Although ERK inhibition completely prevented GM-CSF mRNA stabilization, p38 inhibition had a partial effect. To establish which MAPK was crucial, we transduced pbeos with dominant-active TatMEK1(E) or TatMKK3b(E) proteins that selectively phosphorylate ERK or p38, respectively. These studies showed that ERK but not p38 was sufficient for GM-CSF mRNA stabilization. These data are in contradistinction to the c-Jun NH2-termainal kinase–mediated regulation of interleukin 2 and 3 mRNAs and suggest unique regulatory features for GM-CSF mRNA in eosinophils.

scholarly journals Characteristics of cytokine status in the pathogenesis of experimental periodontitis and immobilization stress

2021 ◽  
Vol 11 (8) ◽  
pp. 504-509
Author(s):  
P. Olekshij
Keyword(s):  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Immobilization Stress ◽  
Interleukin 10 ◽  
Tnf Α ◽  
Experimental Periodontitis ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

The aim of our study is to elucidate changes in the content of pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 (IL-10) in the blood serum of guinea pigs in the dynamics of experimental periodontitis and immobilization stress.The dynamics of the combined pathology (experimental periodontitis and immobilization stress) is accompanied by a pronounced progression of the proinflammatory group of cytokines - TNF-α and IL-6 against the background of declining functional activity of IL-10 at all stages of their formation (3 rd , 5 th and 15 th days) with an advantage on the 15 th day of the experiment. The data obtained indicate an imbalance of pro- and anti-inflammatory cytokines and impaired cytokinogenesis, which is important for the pathogenesis in this combined pathology.

167 THE SUPPLEMENTATION OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) PROMOTES THE DEVELOPMENT OF NUCLEAR TRANSFERRED BOVINE EMBRYOS

2006 ◽  
Vol 18 (2) ◽  
pp. 191
Author(s):  
D. H. Kim ◽  
S. W. Kim ◽  
B. C. Yang ◽  
G. S. Im ◽  
H. S. Park ◽  
...  
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Female Reproductive Tract ◽  
Apoptotic Cells ◽  
Colony Stimulating Factor ◽  
Bovine Embryos ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Granulocyte-macrophage colony stimulating factor (GM-CSF) is secreted by epithelial cells lining the female reproductive tract in mice and several other species. GM-CSF receptors are present in the fertilized oocyte and in all subsequent stages of development, and in blastocysts it is expressed in both inner cell mass and trophectoderm cells. Recent studies suggest that GM-CSF can act as a survival factor for the developing embryo. The purpose of this study was to examine the effect of GM-CSF, as a medium supplement, on the development of nuclear-transferred bovine embryos. Oocytes were enucleated after in vitro maturation in TCM-199 supplemented with 10% fetal bovine serum (FBS), 1 mg/mL FSH, and 1 mg/mL estradiol-17� for 20 h. Enucleated oocytes were fused with bovine ear skin fibroblast cells by a DC pulse of 25 V/150 mm for 20 ms in Zimmerman cell fusion medium. For activation, reconstructed embryos were exposed to 10 mM Ca-ionophore for 5 min, followed by 2 mM 6-dimethylaminopurine for 3 h. NT embryos were subsequently cultured in CR2 medium without or with 10 ng/mL recombinant porcine GM-CSF at 39.0�C in 5% O2, 5% CO2 and 90% N2. After 7 days of culture, blastocyst formation was observed. The number of inner cell mass (ICM) and trophectoderm (TE) cells was examined by differential staining. Apoptotic cells in blastocysts were detected by a terminal deoxynucleotidyl transferase-mediated d-UTP nick-end labeling (TUNEL) assay. Data were analyzed by chi-square and Student's t-test. Addition of GM-CSF to the medium significantly (P < 0.05) increased the proportion of embryos developing to the blastocyst stage (37.6 � 12.0 and 54.7 � 13.9% for control and GM-CSF groups respectively). No differences in the total cell number and the ratio of ICM to total cells were detected between the control group (125.4 � 35.7 and 38.5 � 9.7%) and the GM-CSF group (123.8 � 35.1 and 34.2 � 13.1%). The mean proportion of apoptotic cells in blastocysts was not different between the control (5.4 � 5.4%) and the GM-CSF (5.3 � 3.9%) group. Our results showed the beneficial effect of GM-CSF on the development of NT bovine embryos. These results suggest that GM-CSF might be a useful molecule for increasing development of NT bovine embryos. Further studies are necessary to verify the mechanism of GM-CSF on the development of bovine NT embryos.

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