Interleukin-1β Regulates Lipid Homeostasis in Human Glomerular Mesangial Cells.

Abstract

Recent studies have shown that hyperlipidemia is closely related to the progression of kidney disease and glomerulosclerosis has similar pathophysiological mechanisms with atherosclerosis. Atherosclerosis is essentially a chronic inflammatory process and various kidney diseases are characterized by a micro-inflammatory state. Hyperlipidemia levels are not parallel to the degree of glomerulosclerosis, inflammatory factors together with lipids may contribute to the pathogenesis of glomerulosclerosis. Therefore, it is key to clarify lipid-mediated renal injury through studying the mechanism by which inflammation affects cholesterol homeostasis at the cellular level. Intracellular lipid homeostasis involves both lipid uptake and excretion, therefore in this study, we aimed to explore whether interleukin-1β (IL-1β) promotes the uptake of oxidized low-density lipoprotein (Ox-LDL) to increase in intracellular lipid levels, and to clarify the effect of IL-1β on the expression of lectin-like oxidized LDL receptor 1 (LOX-1) and ATP-binding cassette transporter A1 (ABCA1), which may regulate cholesterol homeostasis in human mesangial cells (HMCs). The effect of IL-1β on uptake of Ox-LDL labeled with fluorescent Dil (Dil-Ox-LDL) by HMCs was observed using laser confocal microscopy. The effect of IL-1β on LOX-1 and ABCA1 expression in HMCs was detected by polymerase chain reaction and western blotting. Laser confocal microscopy revealed that HMCs took up Dil-Ox-LDL. Treatment of HMCs with 5 ng/ml IL-1β for 24 h significantly increased uptake of Dil-Ox-LDL. IL-1β also promoted LOX-1 mRNA and protein expression in a dose-dependent manner. Moreover, ABCA1 mRNA and protein expression were reduced by IL-1β in lipid-loaded HMCs in a dose-dependent manner. IL-1β promotes the uptake of Ox-LDL and expression of LOX-1 in HMCs, whereas it inhibits expression of ABCA1 under lipid load. The imbalance in intracellular cholesterol resulted by IL-1β can in turn transform HMCs into foam cells and aggravate glomerulosclerosis.