Abnormal expression and function of Dectin-1 receptor in type 2 diabetes mellitus patients with poor glycemic control (HbA1c > 8%25)
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Dectin-1 is a key innate receptor involved in various cellular responses and may have a direct role in chronic inflammatory conditions such as type 2 diabetes mellitus. The aim of this work was to evaluate the expression and function of Dectin-1 in peripheral blood mononuclear cells from T2D patients. Dectin-1 expression was analyzed by flow cytometry and RT-PCR in monocytes and lymphocyte subpopulations from T2D patients (n = 34) and healthy subjects (n = 29). Functional assays were used to assess cytokine synthesis, ROS levels and oxidative stress ratio. We found increased expression (MFI) of Dectin-1 in monocytes from T2D patients. Significantly higher Dectin-1 expression was also detected in CD4 T, CD8 T, B cells and NK cells from T2D patients compared to controls. In contrast, monocytes from T2D patients with poor glycemic control (HbA1c > 8%25) showed a diminished percentage of Dectin-1 /TLR2 cells. Negative correlations between the percent of Dectin-1 /TLR2 cells and fasting plasma glucose levels (FPG) and HbA1c levels were found. A significant reduction in basal levels of IL-10 was observed in patients with poor glycemic control (HbA1c > 8%25) compared to patients with appropriate glycemic control (HbA1c ≤ 6.5%25) and healthy controls, an effect that was not observed in monocytes stimulated with zymosan. Higher ROS levels in zymosan-stimulated cells from patients with poor glycemic control positively correlated with FPG levels, and the oxidative stress ratio was higher in T2D cells compared with controls. Our data indicate that Dectin-1 may be involved in the abnormal immune responses that are observed in patients with T2D. © 2012 Elsevier Inc. All rights reserved.
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Dectin-1 is a key innate receptor involved in various cellular responses and may have a direct role in chronic inflammatory conditions such as type 2 diabetes mellitus. The aim of this work was to evaluate the expression and function of Dectin-1 in peripheral blood mononuclear cells from T2D patients. Dectin-1 expression was analyzed by flow cytometry and RT-PCR in monocytes and lymphocyte subpopulations from T2D patients (n = 34) and healthy subjects (n = 29). Functional assays were used to assess cytokine synthesis, ROS levels and oxidative stress ratio. We found increased expression (MFI) of Dectin-1 in monocytes from T2D patients. Significantly higher Dectin-1 expression was also detected in CD4%2b T, CD8%2b T, B cells and NK cells from T2D patients compared to controls. In contrast, monocytes from T2D patients with poor glycemic control (HbA1c > 8%25) showed a diminished percentage of Dectin-1%2b/TLR2%2b cells. Negative correlations between the percent of Dectin-1%2b/TLR2%2b cells and fasting plasma glucose levels (FPG) and HbA1c levels were found. A significant reduction in basal levels of IL-10 was observed in patients with poor glycemic control (HbA1c > 8%25) compared to patients with appropriate glycemic control (HbA1c ≤ 6.5%25) and healthy controls, an effect that was not observed in monocytes stimulated with zymosan. Higher ROS levels in zymosan-stimulated cells from patients with poor glycemic control positively correlated with FPG levels, and the oxidative stress ratio was higher in T2D cells compared with controls. Our data indicate that Dectin-1 may be involved in the abnormal immune responses that are observed in patients with T2D. © 2012 Elsevier Inc. All rights reserved.
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Chronic inflammation; Immunology; Monocytes; Reactive oxygen species CD19 antigen; CD4 antigen; CD56 antigen; CD8 antigen; cytokine; dectin 1 receptor; glucose; hemoglobin A1c; interleukin 10; messenger RNA; reactive oxygen metabolite; receptor protein; toll like receptor 2; unclassified drug; zymosan; adult; article; CD4 T lymphocyte; CD8 T lymphocyte; clinical article; controlled study; cytokine production; diabetic patient; female; flow cytometry; glucose blood level; glycemic control; human; human cell; immune response; lymphocyte subpopulation; male; monocyte; natural killer cell; non insulin dependent diabetes mellitus; oxidative stress; peripheral blood mononuclear cell; priority journal; protein expression; reverse transcription polymerase chain reaction; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Flow Cytometry; Hemoglobin A, Glycosylated; Humans; Lectins, C-Type; Male; Middle Aged; Monocytes; Reactive Oxygen Species; Receptors, Cell Surface; Toll-Like Receptor 2
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Chronic inflammation; Immunology; Monocytes; Reactive oxygen species CD19 antigen; CD4 antigen; CD56 antigen; CD8 antigen; cytokine; dectin 1 receptor; glucose; hemoglobin A1c; interleukin 10; messenger RNA; reactive oxygen metabolite; receptor protein; toll like receptor 2; unclassified drug; zymosan; adult; article; CD4+ T lymphocyte; CD8+ T lymphocyte; clinical article; controlled study; cytokine production; diabetic patient; female; flow cytometry; glucose blood level; glycemic control; human; human cell; immune response; lymphocyte subpopulation; male; monocyte; natural killer cell; non insulin dependent diabetes mellitus; oxidative stress; peripheral blood mononuclear cell; priority journal; protein expression; reverse transcription polymerase chain reaction; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Flow Cytometry; Hemoglobin A, Glycosylated; Humans; Lectins, C-Type; Male; Middle Aged; Monocytes; Reactive Oxygen Species; Receptors, Cell Surface; Toll-Like Receptor 2
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