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Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity.

Abstract：

AIMS/HYPOTHESIS:In type 2 diabetes mellitus (T2DM), the abnormal protein and lipid composition of diabetic high-density lipoprotein (HDL) could impair its anti-inflammatory functions. Whether nonenzymatic glycation directly impaired the anti-inflammatory effects of HDL in innate immunity remained unclear. METHODS:Human acute monocytic leukemia cell line (THP-1) cells, mouse RAW 264.7 macrophages and primary human monocytes derived macrophages were pre-incubated with native HDL, diabetic HDL isolated from T2DM patients or HDL glycated with different doses of d-glucose in vitro and then challenged with lipopolysaccharide (LPS). The release of tumor necrosis factor (TNF)-α and IL-1β was assayed by enzyme-linked immunosorbent assay (ELISA). Phosphorylation of Iκ-Bα in cytoplasm and nuclear translocation of NF-κB were detected by western blot. Glycation levels of native HDL, glycated HDL and diabetic HDL were determined using LC-MS/MS. RESULTS:The potency of diabetic HDL to inhibit the release of TNF-α (p < 0.05) and IL-1β (p < 0.001) was dramatically attenuated compared with that of native HDL. Similarly, glycation of HDL in vitro impaired its ability to inhibit TNF-α and IL-1β release in a glucose dose-dependent manner. Moreover, apoHDL still effectively inhibited the release of TNF-α and IL-1β induced by LPS, but glycated apoHDL partly lost such abilities. Nonenzymatic glycation levels of glycated HDL and diabetic HDL increased 28 fold (p < 0.001) and 4 fold (p < 0.001), respectively compared with that of native HDL. CONCLUSIONS:In this study, we observed that diabetic HDL and HDL glycated in vitro both partly lose their protective effects to inhibit cytokines release induced by LPS in macrophages, and nonenzymatic glycation of the protein components of HDL plays key roles in these impairments.

journal_name

Diabetes Metab Res Rev

journal_title

Diabetes/metabolism research and reviews

authors

Liu D,Ji L,Zhang D,Tong X,Pan B,Liu P,Zhang Y,Huang Y,Su J,Willard B,Zheng L

doi

10.1002/dmrr.1297

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

186-95

issue

eissn

1520-7552

issn

1520-7560

journal_volume

pub_type

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Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity.