Effect of LPS on the level of TLR4 and on the expression of NF-κB and Notch1 in monocytes from patients with type 2 diabetic nephropathy / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
;
(12): 578-585, 2012.
Article
in Chinese
| WPRIM
| ID: wpr-814629
ABSTRACT
OBJECTIVE@#To characterize the expression of Toll-like receptor 4 (TLR4) in monocytes of diabetic nephropathy (DN) patients and the response of TLR4 to lipopolysaccharide (LPS), and, further, to explore the potential effects of inflammatory immune response in DN.@*METHODS@#Thirty DN patients with uremia, ten early-type 2 DN patients, and twenty healthy volunteers were enrolled for the determination of TLR4 expression in monocytes by using peripheral blood flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated and subjected to 1 μg/mL LPS for 24 h. Monocytes were collected to assay NF-κB p65 and Notch1 expression by Western blot, with immuneofluorescence detection. Serum and supernatants were sampled for the determination of interleukin-6 (IL-6) concentration by using ELISA. Serum C-reactive protein (CRP) level was determined by using the immunoturbidimetry.@*RESULTS@#Compared with the normal control, type 2 DN uremic patients had a significantly higher TLR4 fluorescence-blot intensities (FI), and serum CRP and IL-6 levels [TLR4 FI DN uremia patients 2.8±0.9; early type 2 DN patients 3.4 ±0.7; healthy subjects 1.6±0.7. IL-6 concentration DN uremia patients (84.8±20.7) pg/mL; early type 2 DN patients (63.20±14.4) pg/mL; healthy subjects (11.0±2.0) pg/mL. CRP concentraton DN uremia patients (5.4±2.8) mg/L; early type 2 DN patients (3.7±1.7) mg/L; healthy subjects (1.7±0.7) mg/L. P<0.01 for any DN-group vs control]. In early type 2 DN patients, following exposure to LPS, PBMCs showed a significant upregulation in TLR4 and NF-κB p65 expression and a remarked increase in serum IL-6 level (all P<0.05), and NF-κB p65 transfer to the nucleus is enhanced. Notch1 protein expression was not significantly altered in any group.@*CONCLUSION@#A disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in type 2 DN patients. Such immunological dysfunction may be related to activation in NF-κB/TLR4 signaling pathways, and have nothing to do with the Notch1 signaling pathway.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Blood
/
Monocytes
/
Signal Transduction
/
Lipopolysaccharides
/
Diabetes Mellitus, Type 2
/
Diabetic Nephropathies
/
Transcription Factor RelA
/
Toll-Like Receptor 4
/
Receptor, Notch1
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
Language:
Chinese
Journal:
Journal of Central South University(Medical Sciences)
Year:
2012
Type:
Article
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