Modulation of monocyte hyperresponsiveness to TLR ligands by 1,25-dihydroxy-vitamin D3 from LADA and T2DM.
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.
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
Huang
Gan
G
Lin
Jian
J
Yang
Lin
L
Li
Xia
X
Zhou
Wei-Dong
WD
Chao
Chen
C
D000328:Adult; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists* / Q000378:metabolism
D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C009900:lipoteichoic acid; D002117:Calcitriol