Regulation by 1, 25-dihydroxy-vitamin D3 on altered TLRs expression and response to ligands of monocyte from autoimmune diabetes

Background: Altered Toll-like receptors (TLRs) expression and response of monocyte may be associated with insulin sensitivity, obesity and diabetes. Methods: Peripheral blood monocytes were respectively collected from 23 healthy controls, 16 type 1 diabetes mellitus (T1DM), and 18 latent autoimmune diabetes in adults (LADA). CD14, TLR2 and TLR4 expression were analyzed by flow cytometer. Moreover, the effect of 1, 25-dihydroxy-vitamin D3 (11,25 (OH)2,D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation concentration of NF-kappa B-p65 and associated cytokine production. Results: Monocytes showed significantly higher surface CD14 and TLR4 expressions from LADA and lower CD14 expression from T1DM than controls. TLRs ligands decreased monocyte CD14 expression in T1DM but increased in LADA. Monocyte hyperresponsiveness to ligands was modulated by 1,25(OH)(2)D3 to similar concentration, as compared to controls. Conclusions: Monocytes from T1DM and LADA showed similar cellular reactivity towards ligands and 1.25 (OH)2D3 was observed to restore this defect to a certain extent in vitro. (C) 2009 Elsevier B.V. All rights reserved.