scholarly journals Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-κB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line

2003 ◽  
Vol 12 (2) ◽  
pp. 71-78 ◽  
Author(s):  
Ana Luísa Vital ◽  
Margarida Gonçalo ◽  
M. Teresa Cruz ◽  
Américo Figueiredo ◽  
Carlos B. Duarte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
No Production ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Protein Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Oxide Synthase ◽  
Stimulating Factor

Aims:Nitric oxide (NO) has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in a mouse fetal skin dendritic cell line.Methods:NO production was assessed by the method of Griess. Expression of the inducible isoform of nitric oxide synthase (iNOS) protein was evaluated by western blot analysis and immunofluorescence microscopy. Western blot analysis was also performed to evaluate cytosolic IkappaB-alpha (IκB-α) protein levels. The electrophoretic mobility shift assay was used to evaluate the activation or inhibition of nuclear factor kappa B (NF-κB).Results:GM-CSF induced iNOS expression and NO production, and activated the transcription factor NF-κB. Dexamethasone inhibited, in a dose-dependent manner, NO production induced by GM-CSF. Addition of dexamethasone to the culture, 30 min before GM-CSF stimulation, significantly inhibited the cellular expression of iNOS. Dexamethasone also inhibited GM-CSF-induced NF-κB activation by preventing a significant decrease on the IκB-α protein levels, thus blocking NF-κB migration to the nucleus.Conclusions:The corticosteroid dexamethasone inhibits GM-CSF-induced NF-κB activation, iNOS protein expression and NO production. These results suggest that dexamethasone is a potent inhibitor of intracellular events that are involved on NO synthesis, in skin dendritic cells.

scholarly journals Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF after benzene treatment of mice

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3255-3263
Author(s):  
CJ Punjabi ◽  
JD Laskin ◽  
SM Hwang ◽  
L MacEachern ◽  
DL Laskin
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Production ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Oxide Production ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Oxide Synthase ◽  
Stimulating Factor

Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony- stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that was dependent on the presence of an inflammatory mediator and blocked by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMA). Treatment of mice with the hematotoxicant benzene (800 mg/kg, intraperitoneally, two times per day, for 2 days) resulted in a significant increase in nitric oxide production by BM cells stimulated with lipopolysaccharide (LPS) and interferon gamma alone or in combination with M-CSF or GM-CSF. Cells from benzene-treated mice also displayed increased sensitivity to the growth-promoting effects of M-CSF and GM-CSF. These results suggest that benzene treatment of mice primes BM cells to inducers of nitric oxide. Northern blot analysis showed that this was, at least in part, caused by increased expression of mRNA for inducible nitric oxide synthase (iNOS). Surprisingly, treatment of mice with L-NMA was found to cause a depression in BM cell proliferation and to potentiate benzene-induced decreases in BM cellularity and increases in nitric oxide production. L-NMA administration also augmented nitric oxide production by BM cells. These data indicate that L-NMA is hematotoxic and suggest that it may have actions distinct from inhibition of nitric oxide synthase in the BM.

scholarly journals Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF after benzene treatment of mice

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3255-3263 ◽  
Author(s):  
CJ Punjabi ◽  
JD Laskin ◽  
SM Hwang ◽  
L MacEachern ◽  
DL Laskin
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Production ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Oxide Production ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Oxide Synthase ◽  
Stimulating Factor

Abstract Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony- stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that was dependent on the presence of an inflammatory mediator and blocked by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMA). Treatment of mice with the hematotoxicant benzene (800 mg/kg, intraperitoneally, two times per day, for 2 days) resulted in a significant increase in nitric oxide production by BM cells stimulated with lipopolysaccharide (LPS) and interferon gamma alone or in combination with M-CSF or GM-CSF. Cells from benzene-treated mice also displayed increased sensitivity to the growth-promoting effects of M-CSF and GM-CSF. These results suggest that benzene treatment of mice primes BM cells to inducers of nitric oxide. Northern blot analysis showed that this was, at least in part, caused by increased expression of mRNA for inducible nitric oxide synthase (iNOS). Surprisingly, treatment of mice with L-NMA was found to cause a depression in BM cell proliferation and to potentiate benzene-induced decreases in BM cellularity and increases in nitric oxide production. L-NMA administration also augmented nitric oxide production by BM cells. These data indicate that L-NMA is hematotoxic and suggest that it may have actions distinct from inhibition of nitric oxide synthase in the BM.

Role for Bcl-xL in Delayed Eosinophil Apoptosis Mediated by Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-5

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 778-783 ◽  
Author(s):  
Birgit Dibbert ◽  
Isabelle Daigle ◽  
Doris Braun ◽  
Corinna Schranz ◽  
Martina Weber ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Colony Stimulating Factor ◽  
Interleukin 5 ◽  
Gm Csf ◽  
Protein Levels ◽  
Tissue Eosinophilia ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Eosinophil Apoptosis

Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils. © 1998 by The American Society of Hematology.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces antiapoptotic and proapoptotic signals in acute myeloid leukemia

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 630-637 ◽  
Author(s):  
Stefan Faderl ◽  
David Harris ◽  
Quin Van ◽  
Hagop M. Kantarjian ◽  
Moshe Talpaz ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Protein Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Acute Myeloid

AbstractHigh levels of cytokines are associated with a poor prognosis in acute myeloid leukemia (AML). However, cytokines may induce, on one hand, survival factor expression and cell proliferation and, on the other hand, expression of inhibitory signals such as up-regulation of suppressors of cytokine signaling (SOCS) and induce apoptotic cell death. Because blasts from patients with AML express high procaspase protein levels, we asked whether granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances procaspase protein production in AML cells. In the GM-CSF–responsive OCIM2 AML cell line, GM-CSF induced signal transducer and activator of transcription 5 (Stat 5) phosphorylation, up-regulated cyclin D2, and stimulated cell cycle progression. Concurrently, GM-CSF stimulated expression of SOCS-2 and -3 and of procaspases 2 and 3 and induced caspase 3 activation, poly(ADP[adenosine 5′-diphosphate]-ribose) polymerase (PARP) cleavage, and apoptotic cell death. The Janus kinase (Jak)–Stat inhibitor AG490 abrogated GM-CSF–induced expression of procaspase 3 and activation of caspase 3. Under the same conditions GM-CSF up-regulated production of BAX as well as Bcl-2, Bcl-XL, survivin, and XIAP. GM-CSF also increased procaspase 3 protein levels in OCI/AML3 and Mo7e cells, suggesting that this phenomenon is not restricted to a single leukemia cell line. Our data suggest that GM-CSF exerts a dual effect: it stimulates cell division but contemporaneously up-regulates Jak-Stat–dependent proapoptotic proteins. Up-regulation of procaspase levels in AML is thus a beacon for an ongoing growth-stimulatory signal.

scholarly journals Hematopoietic Effects of Paeoniflorin and Albiflorin on Radiotherapy-Induced Myelosuppression Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yingli Zhu ◽  
Linyuan Wang ◽  
Zhihui Yang ◽  
Jingxia Wang ◽  
Wei Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
White Blood Cells ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Protein Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Paeonia lactifloraroot (baishao in Chinese) is a commonly used herb in traditional Chinese medicine (TCM). Paeoniflorin (PF) and albiflorin (AF) are two major active constituents ofP. lactiflora. In this paper, we aimed to investigate the hematopoietic effects of PF and AF on myelosuppression mice induced by radiotherapy and to explore the underlying mechanism. The finding indicated that PF and AF significantly increased the numbers of white blood cells (WBC) and reversed the atrophy of thymus. Furthermore, PF and AF increased the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) and reduced the levels of tumor necrosis factor-α(TNF-α) in serum and increased the level of colony-stimulating factor (G-CSF) in plasma. Lastly, PF and AF not only enhanced the mRNA levels of GM-CSF and G-CSF in the spleens, but also increased the protein levels of G-CSF and GM-CSF in bone marrow. Our results suggest that PF and AF may promote the recovery of bone marrow hemopoietic function in a myelosuppressed mouse model.

Role for Bcl-xL in Delayed Eosinophil Apoptosis Mediated by Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-5

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 778-783 ◽  
Author(s):  
Birgit Dibbert ◽  
Isabelle Daigle ◽  
Doris Braun ◽  
Corinna Schranz ◽  
Martina Weber ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Colony Stimulating Factor ◽  
Interleukin 5 ◽  
Gm Csf ◽  
Protein Levels ◽  
Tissue Eosinophilia ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Eosinophil Apoptosis

Abstract Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils. © 1998 by The American Society of Hematology.

scholarly journals Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jani Lappalainen ◽  
Nicolas Yeung ◽  
Su D. Nguyen ◽  
Matti Jauhiainen ◽  
Petri T. Kovanen ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Foam Cells ◽  
Colony Stimulating Factor ◽  
Human Macrophages ◽  
Gm Csf ◽  
Macrophage Subpopulations ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

AbstractIn atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.

The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns

Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Verena Schulte ◽  
Alexandra Sipol ◽  
Stefan Burdach ◽  
Esther Rieger-Fackeldey
Keyword(s):  
Respiratory Failure ◽  
Peripheral Blood ◽  
Colony Stimulating Factor ◽  
Term Infants ◽  
Respiratory Impairment ◽  
Gm Csf ◽  
A Subunit ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

<b><i>Background:</i></b> The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. β<sub>C</sub> is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. β<sub>IT</sub> is a physiological, truncated isoform of β<sub>C</sub> and is known to act as physiological inhibitor of β<sub>C</sub>. <b><i>Objective:</i></b> The aim of this study was to determine the ratio of β<sub>IT</sub> and β<sub>C</sub> in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. <b><i>Methods:</i></b> We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). β<sub>IT</sub> and β<sub>C</sub> expression were determined in peripheral blood cells by real-time PCR. β<sub>IT</sub> expression, defined as the ratio of β<sub>IT</sub> and β<sub>C</sub>, was correlated with the respiratory score. <b><i>Results:</i></b> β<sub>IT</sub> expression was found in all 59 recruited newborns with a trend toward higher β<sub>IT</sub> in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; <i>p</i> = 0.066). Seriously ill newborns (score 3) had significantly higher β<sub>IT</sub> than healthy newborns ([score 0], <i>p</i> = 0.010). Healthy preterm infants had significantly higher β<sub>IT</sub> expression than healthy term infants (<i>p</i> = 0.019). <b><i>Conclusions:</i></b> β<sub>IT</sub> is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that β<sub>IT</sub> may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of β<sub>C</sub> and, therefore, maintaining surfactant in respiratory ill newborns.

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