Interleukin-1β Promotes Ox-LDL Uptake by Human Glomerular Mesangial Cells via LOX-1

Int J Med Sci. 2020 Apr 27;17(8):1056-1061. doi: 10.7150/ijms.43981. eCollection 2020.

Abstract

The aim of this study was to determine whether interleukin-1β (IL-1β) promotes oxidised low-density lipoprotein (Ox-LDL) uptake by human glomerular mesangial cells (HMCs) and its effect on the expression of lectin-like Ox-LDL receptor 1 (LOX-1) and to identify pathways through which IL-1β affects lipid uptake. Confocal laser scanning microscopy and flow cytometry were used to observe the effect of IL-1β on lipid uptake by HMCs and the pathway by which IL-1β may mediate lipid uptake. Real-time polymerase chain reaction (PCR) and western blotting were used to evaluate the effect of IL-1β on LOX-1 expression. Confocal laser scanning microscopy and flow cytometry revealed that IL-1β promoted uptake of fluorescent Dil-labelled Ox-LDL(Dil-Ox-LDL) by HMCs and the enhanced uptake of Dil-Ox-LDL was partially inhibited by an anti-LOX-1 antibody evaluated by flow cytometry. Further, IL-1β promoted LOX-1 mRNA and protein expression of HMCs in a dose- and time-dependent manner. Thus, Ox-LDL is ingested by HMCs under basic conditions. Inflammatory cytokine IL-1β promotes Ox-LDL uptake by HMCs. Furthermore, IL-1β promotes the mRNA and protein expression of LOX-1, a specific receptor of Ox-LDL, suggesting that the enhancement of Ox-LDL uptake may be mediated by LOX-1 pathway. Anti-LOX-1 therapy may be a promising option for treatment of glomerulosclerosis.

Keywords: Interleukin-1β; lectin-like Ox-LDL receptor 1; oxidised low-density lipoprotein.

MeSH terms

  • Cell Line
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / immunology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Flow Cytometry
  • Humans
  • Interleukin-1beta / metabolism*
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / immunology
  • Lipoproteins, LDL / metabolism*
  • Mesangial Cells / immunology
  • Mesangial Cells / metabolism*
  • Mesangial Cells / ultrastructure
  • Microscopy, Confocal
  • Scavenger Receptors, Class E / antagonists & inhibitors
  • Scavenger Receptors, Class E / metabolism*

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • Lipoproteins, LDL
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein