scholarly journals The role of eosinophilopoietins and integrins on eosinophils biology in asthma

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Jolita Palacionyte ◽  
Andrius Januškevičius ◽  
Kęstutis Malakauskas
Keyword(s):  
Biological Significance ◽  
Airway Disease ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Inflammatory Airway Disease ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Type 2 Inflammation

Asthma is a chronic inflammatory airway disease that affects about 300 million peopleworldwide, and the incidence is continuously increasing. Patientswith asthma aremost commonly diagnosedwith type 2 inflammation,which is characterized by eosinophilia, which is an increased amount of eosinophils in the blood and airways. Asthma with predominant eosinophilic inflammation is characterized by amore severe course of the disease,more frequent exacerbations, andmore intense symptoms. To reduce symptoms, facilitate the course of the disease, and treat asthma more effectively is important to understand asthma pathogenesis better. Eosinophils survivalmaturation, activation, and quantity in the lungs are promoted by cytokines, of which eosinophilopoietins – interleukin (IL) 3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are themost important. Eosinophilia is also associated with the activation of integrins present on the surface of eosinophils. Integrins areresponsible for eosinophils adhesion to airway structural cells, thus prolonging their survival leading to more intense airway eosinophilia. Eosinophilopoietins, their receptors, and integrins might be suitable targets reducing eosinophilia in blood and airway, as well as airway inflammation.Humanizedmonoclonal antibodies are used for this purpose. Biological therapy allows for the specific inhibition of relevant asthma pathways and offers patients individualized treatment. This review will discuss the biological significance of eosinophilopoietins and their receptors, integrins on eosinophils functions, anti-cytokine and anti-integrin therapy efficiency in asthma.

scholarly journals Probiotic-Based Therapy for Active Tuberculosis Infection: The Role of Gut-Lung Axis and Granulocyte Macrophage-Colony Stimulating Factor

2021 ◽  
Vol 7 (2) ◽  
pp. 93
Author(s):  
Made Indira Dianti Sanjiwani ◽  
Nyoman Budhi Wirananda Setiawan ◽  
Agus Indra Yudhistira Diva Putra ◽  
Agus Eka Darwinata
Keyword(s):  
Potential Role ◽  
Active Tuberculosis ◽  
Tuberculosis Infection ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Global Health Problem

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.

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.

Role of Protein Kinase C in Expression of Granulocyte Colony Stimulating Factor and Granulocyte-Macrophage Colony Stimulating Factor in Lung Cancer Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4210-4210
Author(s):  
Yoshiki Uemura ◽  
Makoto Kobayashi ◽  
Hideshi Nakata ◽  
Tetsuya Kubota ◽  
Hirokuni Taguchi
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Kinase C ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

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

The Ig-like domain of human GM-CSF receptor α plays a critical role in cytokine binding and receptor activation

2010 ◽  
Vol 426 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Shamaruh Mirza ◽  
Andrew Walker ◽  
Jinglong Chen ◽  
James M. Murphy ◽  
Ian G. Young
Keyword(s):  
Structural Alignment ◽  
Critical Role ◽  
Receptor Activation ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Subsequent Activation ◽  
Macrophage Colony ◽  
Key Residues ◽  
Stimulating Factor

GM-CSF (granulocyte/macrophage colony-stimulating factor) is an important mediator of inducible haemopoiesis and inflammation, and has a critical role in the function of alveolar macrophages. Its clinical applications include the mobilization of haemopoietic progenitors, and a role as an immune stimulant and vaccine adjuvant in cancer patients. GM-CSF signals via a specific α receptor (GM-CSFRα) and the shared hβc (human common β-subunit). The present study has investigated the role of the Ig-like domain of GM-CSFRα in GM-CSF binding and signalling. Deletion of the Ig-like domain abolished direct GM-CSF binding and decreased growth signalling in the presence of hβc. To locate the specific residues in the Ig-like domain of GM-CSFRα involved in GM-CSF binding, a structural alignment was made with a related receptor, IL-13Rα1 (interleukin-13 receptor α1), whose structure and mode of interaction with its ligand has recently been elucidated. Mutagenesis of candidate residues in the predicted region of interaction identified Val51 and Cys60 as having critical roles in binding to the α receptor, with Arg54 and Leu55 also being important. High-affinity binding in the presence of hβc was strongly affected by mutation of Cys60 and was also reduced by mutation of Val51, Arg54 and Leu55. Of the four key residues, growth signalling was most severely affected by mutation of Cys60. The results indicate a previously unrecognized role for the Ig-like domain, and in particular Cys60, of GM-CSFRα in the binding of GM-CSF and subsequent activation of cellular signalling.

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