scholarly journals Granulocyte-Macrophage Colony-Stimulating Factor Protects Dimethylnitrosamine-Induced Rat Liver Fibrosis By Inhibiting Transforming Growth Factor-β1 Signaling Pathway

2021 ◽  
Author(s):  
Mrigendra Bir Karmacharya ◽  
Binika Hada ◽  
So Ra Park ◽  
Kil Hwan Kim ◽  
Byung Hyune Choi
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Inhibitory Effects ◽  
Gm Csf ◽  
Ppar Γ ◽  
Rat Liver Fibrosis ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Tgf Β1

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts several therapeutic pharmacological effects but its role in liver fibrosis has not yet been studied. The current study investigates the inhibitory effects of GM-CSF on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. In this study, liver fibrosis was induced in Sprague-Dawley rats by intraperitoneal injections of DMN (10 mg/kg of body weight) for three consecutive days per week for four weeks. To see the inhibitory effects on disease onset, GM-CSF (50 µg/kg of body weight) was injected for 2 consecutive days per week for 4 weeks along with DMN, while to see the therapeutic effects on disease progression, the GM-CSF injection was set forth at 4 weeks after the DMN injection. We found that DMN administration produced characteristics of molecular and pathological manifestations of liver fibrosis in rats including increased expressions of collagen I, alpha-smooth muscle actin (α-SMA), and transforming growth factor beta 1 (TGF-β1), and decreased PPAR-γ expression. Similarly, elevated serum levels of aspartate aminotransferase (AST), total bilirubin level (TBIL), and decreased albumin level (ALB) were observed. Treatment with GM-CSF improved the pathological liver conditions and significantly inhibited the elevated AST and TBIL, and increased ALB serum levels to normal. GM-CSF significantly decreased collagen I, α-SMA, and TGF-β1 expression and increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. In conclusion, GM-CSF reduced the DMN-induced rat liver fibrosis by inhibiting TGF-β1 signaling pathway.

scholarly journals Role of Granulocyte-Macrophage Colony-Stimulating Factor in Acute Myeloid Leukemia/Myelodysplastic Syndromes

2018 ◽  
pp. 1-6
Author(s):  
Neemat M. Kassem ◽  
Alya M. Ayad ◽  
Noha M. El Husseiny ◽  
Doaa M. El-Demerdash ◽  
Hebatallah A. Kassem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Acute Myeloid

Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. Patients and Methods Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. Results There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti–GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. Conclusion Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans

2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Diego Fiume ◽  
Ilaria Lenci ◽  
Martina Milana ◽  
Tommaso M. Manzia ◽  
Renato Massoud ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Regeneration ◽  
Liver Tumor ◽  
Stem Cell Factor ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Background: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). Aim: To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Methods: Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. Results: GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). Conclusions: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

scholarly journals Granulocyte-macrophage colony-stimulating factor-dependent growth and erythropoietin-induced differentiation of a human cell line MB-02

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2860-2871 ◽  
Author(s):  
DA Morgan ◽  
DL Gumucio ◽  
I Brodsky
Keyword(s):  
Cell Line ◽  
Transforming Growth Factor ◽  
Beta Globin ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Gamma Globin ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Dependent Growth ◽  
Stimulating Factor

Abstract Peripheral blood blasts from a patient with acute megakaryoblastic leukemia were placed into liquid cultures with recombinant growth factors. Growth, but not differentiation, was supported by interleukin- 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the first 30 days of culture. Sustained growth occurred only with GM-CSF and gave rise to the cell line MB-02, which has been in continuous culture for over 1 year. The cell line retained the surface phenotype of the leukemic megakaryoblasts except for the loss of glycoproteins Ib and IIb/IIIa, which were induced after exposure to phorbol esters. The induction of erythropoiesis occurred when GM-CSF- deprived cells were cultured with erythropoietin (Epo). Well-defined morphologic stages of differentiation ranging from primitive erythroblasts to nuclei-extruding normoblasts were seen. Transforming growth factor-beta inhibited GM-CSF- and Epo-dependent growth, but not erythroid maturation. Indirect immunofluorescence using globin chain- specific monoclonal antibodies detected fetal, but not adult hemoglobin in the uninduced cells. beta-globin was induced and gamma-globin was increased after Epo exposure. Both globin species accumulated in the developing erythrocytes until terminal differentiation. Quantitative S1 analysis of beta-like globin transcripts showed very low levels of epsilon- and beta-globin expression and high levels of gamma-globin expression in cells maintained in GM-CSF. Five days after induction with Epo, epsilon message decreased to barely detectable levels while gamma and beta transcripts increased threefold and 20-fold, respectively. This novel cell line not only retains many characteristics of the leukemic megakaryoblasts from which it was derived, but also can be induced to recapitulate apparent normal erythropoiesis.

scholarly journals Bone marrow and splenic granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta mRNA levels in irradiated mice

Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2130-2136 ◽  
Author(s):  
CM Chang ◽  
A Limanni ◽  
WH Baker ◽  
ME Dobson ◽  
JF Kalinich ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Gm Csf ◽  
Protein Levels ◽  
Macrophage Colony Stimulating Factor ◽  
Growth Factor Beta ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of a myeloablative sublethal 775 cGy 60C gamma radiation exposure on endogenous bone marrow (BM) and splenic granulocyte- macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) mRNA levels were assayed in B6D2F1 female mice. BM and spleen were harvested from normal mice and irradiated mice on days 2, 4, 7, 10, and 14 after exposure. Cytokine mRNA levels were determined using reverse transcription-polymerase chain reaction. After irradiation, GM-CSF mRNA levels were significantly increased in the BM from days 2 to 10 and in the spleen from days 4 to 10. However, when BM and splenic GM-CSF protein levels were measured using Western dot blot, no increased protein levels were detected. Serum GM-CSF levels were likewise unchanged. Radiation exposure did not affect BM or splenic TGF- beta mRNA levels and this cytokine is known to be produced by cell populations similar to those that produce GM-CSF. These data suggest that radiation injury to hemopoietic tissues results in differential effects on GM-CSF and TGF-beta mRNA levels and that, in the case of GM- CSF, increased mRNA levels are not matched by increased protein production.

scholarly journals Infusion of Kupffer Cells Expanded in Vitro Ameliorated Liver Fibrosis in a Murine Model of Liver Injury

2021 ◽  
Vol 30 ◽  
pp. 096368972110040
Author(s):  
Weina Li ◽  
Fei He
Keyword(s):  
Liver Fibrosis ◽  
Kupffer Cells ◽  
Critical Role ◽  
Gm Csf ◽  
M2 Polarization ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Cluster Of Differentiation ◽  
Stimulating Factor

Transfer of exogenous macrophages represents an alternative technique to treat liver fibrosis. At present, bone marrow-derived monocytes and stem cells are the main sources for exogenous macrophages. Kupffer cells (KCs) are the resident macrophages in the liver and play a critical role in the liver homeostasis and diseases. It is unclear whether infusion of KCs can treat liver fibrosis. In this study, we observed that granulocyte-macrophage colony stimulating factor (GM-CSF) could improve the purity of cultured KCs and significantly up-regulate the expression of Cluster of Differentiation 11b (CD11b). The most important point is that GM-CSF could significantly promote the proliferation of KCs in vitro. KCs expanded in vitro still had the potential of M1/M2 polarization and phagocytosis. Furthermore, infusion of these KCs could ameliorate liver fibrosis induced by carbon tetrachloride (CCl4) in mice. Together, our results suggest that KCs are likely to be another source for macrophage therapy.

scholarly journals Cytokine therapy with gene-transfected cells: single injection of irradiated granulocyte-macrophage colony-stimulating factor-transduced cells accelerates hematopoietic recovery after cytotoxic chemotherapy in mice

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2960-2965 ◽  
Author(s):  
FM Rosenthal ◽  
R Fruh ◽  
R Henschler ◽  
H Veelken ◽  
P Kulmburg ◽  
...  
Keyword(s):  
Serum Levels ◽  
Cytotoxic Chemotherapy ◽  
Cytokine Therapy ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Hematopoietic Recovery ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Development of cell-based delivery systems that can release therapeutic levels of hematopoietic growth factors into the systemic circulation would facilitate treatment of patients requiring cytokine therapy. In this study, we have investigated the potential of granulocyte- macrophage colony-stimulating factor (GM-CSF)-secreting, irradiated syngeneic murine cells to accelerate hematopoietic recovery after cytotoxic chemotherapy. As a model, CMS-5 fibrosarcoma cells, were transduced with a retroviral vector containing the murine GM-CSF cDNA. Transduced cells secreted 38 ng GM-CSF/10(6) cells in 24 hours. After irradiation, in vitro GM-CSF production initially increased up to fivefold and was measurable for about 2 weeks. One and 2 days after injection of irradiated, GM-CSF-secreting CMS-5 cells (N2/CMVGM- CSF/CMS5 # 6 cells) into mice, GM-CSF serum levels of 405 +/- 58 pg/mL and 183 +/- 36 pg/mL were measured, respectively. Serum levels were comparable with levels detected 3 hours after injection of 100 ng recombinant murine GM-CSF (rmGM-CSF) subcutaneously (90 pg/mL). Injection of N2/CMVGM-CSF/CMS5 # 6 cells in cyclophosphamide-treated mice was as effective in accelerating neutrophil recovery as twice daily subcutaneous injections of rmGM-CSF. These data suggest that irradiated hematopoietic growth factor-secreting cells might offer an alternative to parenteral injections of recombinant cytokines in the treatment of neutropenic patients.

Serum Levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in a Group of Patients with Systemic Sclerosis

1996 ◽  
Vol 9 (1) ◽  
pp. 9-12 ◽  
Author(s):  
A. Riccio ◽  
M. De Caterina ◽  
D. Natale ◽  
E. Grimaldi ◽  
G. Pronesti ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Control Group ◽  
Age Group ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

In this report we investigate the behaviour of the serum levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in the course of Systemic Sclerosis (SS). This cytokine is produced mainly by T and NK cells, and its possible role in the pathogenesis of SS has not been previously described in the literature. Serum GM-CSF levels were assayed in 10 female patients, ageing from 35 to 70, affected by SS. These patients were not suffering from other disorders and were not being treated with steroids or immunosuppressive drug. A solid phase immunoenzymatic method was used to assess the serum levels of GM-CSF. Reference values were previously determined in a control group of 36 healthy women blood donors (19 premenopausal and 17 postmenopausal) (x̄=20.1 ±12.3 pg/ml). All the patients but one showed significantly increased serum levels of GM-CSF (x̄= 120.9 ±125.5 pg/ml). The highest levels were found in the two oldest patients, who also had the longest clinical history of SS, but a clear correlation with age, disease duration or clinical manifestations was not evident, even if the postmenopausal age group patients showed a higher mean value of GM-CSF (x̄= 148.0±144.1 pg/ml) than that found in the premenopausal age group (x̄= 57.7±1.4 pg/ml) (in contrast with the findings in the control group). The absence of other pathogenic conditions in our patients suggests that the increase in serum levels of GM-CSF might be linked to the fibroblast proliferation which is typical of SS. However, our results do not explain the role played by this factor in the fibroblastic proliferation process and an in vitro study is necessary to clarify this aspect.

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