Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane-bound and soluble human leucocyte antigen-G (sHLA-G) molecules display immunotolerant properties favouring tumour cell escape from immune surveillance. sHLA-G molecules have been detected in several tumour pathologies; this study aimed to evaluate sHLA-G expression in lymphoproliferative disorders. sHLA-G plasma level was significantly increased in 110 of 178 newly diagnosed lymphoid proliferations cases i.e. 59% of chronic lymphocytic leukaemia, 65% of B non-Hodgkin lymphomas (NHL) and 58% of T-NHL. To assess the mechanisms involved in this secretion, the differential effect of cytokines was tested in in vitro cultures of NHL cells. A significant induction of sHLA-G level was shown in T-NHL in contrast with B-NHL and normal equivalent cells, after cytokine stimulation with (i) interferongamma (IFNgamma), interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor, (ii) IL-10 and (iii) transforming growth factor beta. An impact of microenvironment on sHLA-G expression was found in B-NHL as shown by the in vitro effect of addition of normal monocytes. Finally, a functional effect of sHLA-G molecules purified from pathologic plasma was demonstrated by their strong capacity to inhibit T-cell proliferation at concentrations currently observed during these disorders. These results suggest that functional sHLA-G molecules are upregulated in lymphoproliferative disorders which can support their potential immunomodulatory role during this pathology.
 ...
PMID:Expression of functional soluble human leucocyte antigen-G molecules in lymphoproliferative disorders. 1759 27

Human in vitro generated dendritic cells and the exosomes they release are potential tools for the modulation of immune responses. Here, we characterized differently generated monocyte-derived dendritic cells (MDDCs) and their exosomes. Culturing of peripheral CD14+ cells from the same individuals with either interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (conventional MDDCs) or alternatively with IL-4 and IL-3 generated immature MDDCs in 7 days. Fluorescence-activated cell sorting (FACS) analysis showed that the IL-4/IL-3-generated MDDCs had significantly lower percentages of CD1a+, CD40+ and CD80+ cells and a higher percentage of CD86+ cells as compared with conventional MDDCs. In addition, IL-4/IL-3-generated MDDCs had significantly higher densities of major histocompatibility complex (MHC) class I [human leucocyte antigen (HLA)-ABC], MHC class II (HLA-DR), CD11c and the tetraspanin CD81 as compared with conventional MDDCs. In a comparison of their ability to stimulate CD8+ T cells, we found that the IL-4/IL-3 MDDCs were slightly more efficient than the conventional MDDCs at inducing interferon (IFN)-gamma release in response to viral peptides. Exosome morphology was confirmed by electron microscopy and exosome phenotypes were analysed by flow cytometry and western blot. In comparison to exosomes from conventional MDDCs, exosomes from IL-4/IL-3-generated MDDCs showed significantly stronger signals for HLA-ABC, HLA-DR, CD11c, CD63 and CD81. Thus, phenotypically the exosomes largely reflected their MDDCs of origin. When exosomes were loaded with viral peptides, both types of exosomes induced IFN-gamma release from CD8+ T cells. Our findings might have significance for the development of DC- and exosome-based therapies.
 ...
PMID:Different types of in vitro generated human monocyte-derived dendritic cells release exosomes with distinct phenotypes. 1794 17


<< Previous 1 2