lipoteichoic-acid and Diabetes-Mellitus--Type-2

To investigate the differences of Toll-like receptors (TLRs) expression and response of monocyte and modulation of 1,25-dihydroxy-vitamin D3 on monocyte activity. Peripheral blood monocytes were collected from 23 healthy controls, 18 latent autoimmune diabetes in adults (LADA), and 22 type 2 diabetes mellitus (T2DM), respectively. CD14, TLR2 and TLR4 expression were analyzed. Moreover, the effect of 1,25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation level of NF-kappaB-p65 and associated cytokine production. Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. The modulation of 1,25(OH)(2)D3 on monocytes makes us to consider more potency of vitamin D3 as therapy in LADA and T2DM.

Topics: Adult; Calcitriol; Cells, Cultured; Cytotoxicity, Immunologic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Female; Humans; Ligands; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Monocytes; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors

Type 2 diabetes mellitus is associated with an increased risk of cardiovascular diseases and accelerated atherosclerosis, which has been associated to hyperglycemia and chronic inflammation. Activated macrophages are described to participate in atherosclerosis due to foam cell formation and pro-inflammatory mediators production. Bacterial infections are described to accelerate atherosclerosis, moreover, gram-positive and negative bacterial DNA was described in atherosclerotic plaques.. We studied the glucose modulation of RAW 264.7 macrophages activation by the gram-positive bacterial antigen lipoteichoic acid (LTA), evaluating nitrite production, tumor necrosis factor alpha secretion and matrix metalloproteinase 9 activity.. High glucose increased macrophages activation by LTA, evidenced by exacerbated nitric oxide and tumor necrosis factor alpha production, as well matrix metalloproteinase 9 secretion.. These effects could contribute to atherosclerotic risk parameters, like atherome plaque instability, and participate in chronic inflammation present in type 2 diabetes.

Topics: Animals; Atherosclerosis; Cell Line; Cytokines; Diabetes Mellitus, Type 2; Electrophoresis, Polyacrylamide Gel; Glucose; Inflammation Mediators; Lipopolysaccharides; Macrophage Activation; Macrophages; Matrix Metalloproteinase 9; Mice; Nitric Oxide; Staphylococcus aureus; Teichoic Acids; Tumor Necrosis Factor-alpha