Oxidized high-density lipoprotein enhances inflammatory activity in rat mesangial cells.
OBJECTIVE
Inflammation is a mechanism of glomerular damage in chronic glomerulopathies, in which dyslipidaemia plays an important role. Unlike native high-density lipoprotein (HDL), oxidized HDL is thought to be an adverse factor in chronic ischaemic disease and may increase the production of inflammatory cytokines in atheromatous plaques and plasma, but the effect of oxidized HDL on mesangial cells remains unclear.


METHODS
Intracellular reactive oxygen species level was measured. The inflammatory and proapoptotic effects of oxidized HDL were detected in rat mesangial cells by measuring levels of tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted, monocyte chemoattractant protein-1, CXC chemokine ligand-1 and early apoptosis. The expression of mitogen-activated protein kinase (MAPK) (p38/MAPK, extracellular-regulated kinase/MAPK and c-Jun N-terminal kinase/MAPK), nuclear factor-kappaB activity and lipoprotein scavenger receptors (CD36, low-density lipoprotein receptor-1 and scavenger receptor BI) were also detected.


RESULTS
Oxidized HDL enhanced reactive oxygen species production and upregulated expression of proinflammatory factors, including tumour necrosis factor-alpha, regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 and CXC chemokine ligand-1 by rat mesangial cells dose in a dependent fashion. Incubation with oxidized HDL also increased rat mesangial cells apoptosis in a dose-dependent manner. These effects partly depended on scavenger receptors CD36 and low-density lipoprotein receptor-1, but not scavenger receptor BI. In addition, co-culture with oxidized HDL activated P38/MAPK, extracellular-regulated kinase (ERK)/MAPK and nuclear factor-kappaB (NF-kappaB).


CONCLUSIONS
The results of the present study suggest that oxidized HDL enhanced proinflammatory properties in mesangial cells partly via CD36 and low-density lipoprotein receptor-1. MAPK and nuclear factor-kappaB pathways were involved in the process. The ability of oxidized HDL to negatively influence mesangial cell biology may represent an important mechanism of chronic kidney disease.
Zhang
Miao
M
Department of Medicine, Drum Tower Hospital, Nanjing University Medical School, People's Republic of China.
Gao
Xiang
X
Wu
Jianxiang
J
Liu
Dongmei
D
Cai
Houan
H
Fu
Lili
L
Mei
Changlin
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018955:CD36 Antigens / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018955:CD36 Antigens; C008132:Cd36 protein, rat; D018932:Chemokine CCL2; D008075:Lipoproteins, HDL; D016328:NF-kappa B; C495136:OLR1 protein, rat; D017382:Reactive Oxygen Species; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases