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

• Published in: Diabetes/metabolism research and reviews 2012-02, Vol.28 (2), p.186-195
• Main Authors: Liu, Donghui, Ji, Liang, Zhang, Dongmei, Tong, Xunliang, Pan, Bing, Liu, Pinli, Zhang, Youyi, Huang, Yining, Su, Jinzi, Willard, Belinda, Zheng, Lemin
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - antagonists & inhibitors; Anti-Inflammatory Agents - pharmacology; Cell Line; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Glucose - chemistry; glycation; Glycosylation; HDL; Humans; Immunity, Innate; inflammation; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - secretion; Lipoproteins, HDL - metabolism; Mice; Tumor Necrosis Factor-alpha - secretion; type 2 diabetes mellitus
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.1297

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