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 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation concentration of NF-kappaB-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.
Du
Tao
T
Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Zhou
Zhi-Guang
ZG
You
Shuo
S
Lin
Jian
J
Yang
Lin
L
Zhou
Wei-Dong
WD
Huang
Gan
G
Chao
Chen
C
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C009900:lipoteichoic acid