PMID- 21928330
OWN - NLM
STAT- MEDLINE
DCOM- 20120622
LR  - 20220321
IS  - 1520-7560 (Electronic)
IS  - 1520-7552 (Linking)
VI  - 28
IP  - 2
DP  - 2012 Feb
TI  - Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory 
      effects in innate immunity.
PG  - 186-95
LID - 10.1002/dmrr.1297 [doi]
AB  - 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)-alpha and IL-1beta was assayed by 
      enzyme-linked immunosorbent assay (ELISA). Phosphorylation of Ikappa-Balpha in cytoplasm 
      and nuclear translocation of NF-kappaB 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-alpha 
      (p < 0.05) and IL-1beta (p < 0.001) was dramatically attenuated compared with that 
      of native HDL. Similarly, glycation of HDL in vitro impaired its ability to 
      inhibit TNF-alpha and IL-1beta release in a glucose dose-dependent manner. Moreover, 
      apoHDL still effectively inhibited the release of TNF-alpha and IL-1beta 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.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Liu, Donghui
AU  - Liu D
AD  - The Institute of Cardiovascular Sciences and Key Laboratory of Molecular 
      Cardiovascular Sciences, Ministry of Education, Peking University Health Science 
      Center, Beijing, China.
FAU - Ji, Liang
AU  - Ji L
FAU - Zhang, Dongmei
AU  - Zhang D
FAU - Tong, Xunliang
AU  - Tong X
FAU - Pan, Bing
AU  - Pan B
FAU - Liu, Pinli
AU  - Liu P
FAU - Zhang, Youyi
AU  - Zhang Y
FAU - Huang, Yining
AU  - Huang Y
FAU - Su, Jinzi
AU  - Su J
FAU - Willard, Belinda
AU  - Willard B
FAU - Zheng, Lemin
AU  - Zheng L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*antagonists & inhibitors/pharmacology
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/blood/*metabolism
MH  - Glucose/chemistry
MH  - Glycosylation
MH  - Humans
MH  - *Immunity, Innate
MH  - Interleukin-1beta/antagonists & inhibitors/metabolism
MH  - Lipoproteins, HDL/*metabolism
MH  - Mice
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2011/09/20 06:00
MHDA- 2012/06/23 06:00
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/06/23 06:00 [medline]
AID - 10.1002/dmrr.1297 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2012 Feb;28(2):186-95. doi: 10.1002/dmrr.1297.