Oxidized high-density lipoprotein enhances inflammatory activity in rat mesangial cells.

AIMS

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.