scholarly journals Pivotal Roles of GM-CSF in Autoimmunity and Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Aoi Shiomi ◽  
Takashi Usui

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+T cells. Therefore, the mechanism of GM-CSF-producing CD4+T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review.

2021 ◽  
Vol 7 (2) ◽  
pp. 93
Author(s):  
Made Indira Dianti Sanjiwani ◽  
Nyoman Budhi Wirananda Setiawan ◽  
Agus Indra Yudhistira Diva Putra ◽  
Agus Eka Darwinata

Tuberculosis is a global health problem with a total of 1.4 million cases in 2015. Over the last decade, several studies have demonstrated the potential role of gut-lung axis in the treatment of tuberculosis. The exact mechanism of the gut-lung axis on tuberculosis is still unknown, however modulation of the gut-lung axis can be performed via probiotic administration. The administered probiotics are capable of inducing an immunomodulating effect which helps in the process of tuberculosis infection. One of the molecules that can be activated with probiotics and plays a role in tuberculosis infection is granulocyte macrophage-colony stimulating factor (GM-CSF). GM-CSF can control intracellular production of M. tuberculosis, inflammation in granulomas, and lung tissue reparation. This article aimed to explore the role of the gut-lung axis, GM-CSF, and the potential of probiotic-based therapy on active tuberculosis infection. It was found that probiotics mediate the immune response via the activation of several inflammatory cytokines and interleukins related to lung infection, but not directly with the tuberculosis pathogen. Thus, probiotic-based therapy has the potential to increase immunity during active tuberculosis infection. Further studies to explore the other mechanisms of the gut-lung axis against tuberculosis through probiotic administration need to be performed.


2018 ◽  
pp. 1-6
Author(s):  
Neemat M. Kassem ◽  
Alya M. Ayad ◽  
Noha M. El Husseiny ◽  
Doaa M. El-Demerdash ◽  
Hebatallah A. Kassem ◽  
...  

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.


Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 971-979 ◽  
Author(s):  
T Tsuda ◽  
D Wong ◽  
J Dolovich ◽  
J Bienenstock ◽  
J Marshall ◽  
...  

Abstract We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4210-4210
Author(s):  
Yoshiki Uemura ◽  
Makoto Kobayashi ◽  
Hideshi Nakata ◽  
Tetsuya Kubota ◽  
Hirokuni Taguchi

Abstract Many cases of tumors that produce granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) have been reported. However, the biological properties regulatory mechanisms of the overproduction of G-CSFor GM-CSF by tumor cells are not well known. We present the role of protein kinase C (PKC) pathways in the constitutive expression of G-CSF and GM-CSF by lung cancer cells. We previously established two lung cancer cell lines, OKa-C-1 and MI-4, that constitutively produce an abundant dose of G-CSF and GM-CSF. We showed that the PKC activator; phorbol 12-myristate 13-acetate (PMA) stimulated the production of GM-CSF in a dose-dependent manner and inversely reduced G-CSF in the cell lines. These effects of PMA were antagonized by PKC inhibitor; staurosporine. The induction of GM-CSF expression by PMA was mediated through the activations of nuclear factor (NF)-kB activation. The induction of G-CSF expression by staurosporine was mediated through p44/42 mitogen-activated protein kinase (MAPK) pathway signaling. PMA accelerated cell growth and inhibited cell death in the cell line. Whereas staurosporine acted inversely. GM-CSF induced by PMA might stimulate cell growth and suppress cell death. G-CSF expression by staurosporine appears to be related to the activation of p44/42 MAPK, and GM-CSF by PMA to NF-kB in OKa-C-1 and MI-4 cells. Figure Figure


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