ABSTRACT
INTRODUCTION: Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure. MATERIALS AND METHODS: Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups. RESULTS: The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p < 0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group. CONCLUSION: The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases
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Subject(s)
Humans , Male , Female , Alternaria/immunology , Alternaria/isolation & purification , Dendritic Cells/immunology , Th2 Cells/immunology , Th2 Cells/pathology , Th17 Cells/immunology , Asthma/immunology , Asthma/pathology , Lipopolysaccharide Receptors/analysis , Phagocytosis/immunology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Flow Cytometry/methods , Leukocytes, Mononuclear/immunology , Dendritic Cells/pathology , Th17 Cells/pathology , Fungi/immunology , Fungi/isolation & purification , Fungi/pathogenicityABSTRACT
INTRODUCTION: Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure. MATERIALS AND METHODS: Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups. RESULTS: The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group. CONCLUSION: The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.
Subject(s)
Alternaria/immunology , Alternariosis/immunology , Asthma/immunology , Dendritic Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Antigens, CD/metabolism , Cell Differentiation , Cells, Cultured , Cytokines/metabolism , Environmental Exposure/adverse effects , Humans , Immunophenotyping , Monocytes/immunology , PhagocytosisABSTRACT
In recent years, cell transplantation has become a focus of attention and reliable outcomes have been achieved in regeneration of the sciatic nerve. The effect of undifferentiated bone marrow stromal cells (BMSCs) on peripheral nerve regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an inside-out vein graft (IOVG) filled with undifferentiated BMSCs (2 × 10(7)cells/ml). In the control group, the vein was filled with phosphate buffer saline alone. The regenerated fibres were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on functional (walking track analysis), histomorphometric and immunohistochemical (Schwann cell detection by S100 expression) criteria. The functional study confirmed significant recovery of regenerated axons in the IOVG/BMSC group (P<0.05). Quantitative morphometric analyses of regenerated fibres showed the number and diameter of myelinated fibres in the IOVG/BMSC group were significantly higher than in the control group (P<0.05). This demonstrates the potential for using undifferentiated BMSCs in peripheral nerve regeneration without the limitations of donor-site morbidity associated with isolation of Schwann cells. It also reduces costs because the interval between tissue collection and cell injection is reduced and the laboratory procedures are simpler compared to undifferentiated BMSCs.
