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

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.

Signaling pathways of chronic kidney diseases, implications for therapeutics

“…88 Increased scavenger receptors, such as lectin-like-oxidized LDL receptor 1 (LOX1), CD36, scavenger receptor-A1 (SR-A1), and SR-A2 in CKD mediate the increased uptake of ox-LDL, leading to the activation of inflammatory signaling pathways. 89,90 Increased ApoC-III levels and reduced ApoC-II to ApoC-III ratio block the activity of LPL and hepatic triglyceride lipase that mediate the conversion of VLDL to intermediate-density lipoprotein (IDL) and IDL to LDL, respectively. This process increases the production of LDL.…”

Conbercept enhances the phagocytic activity of retinal Müller glia towards hard exudates in diabetic retinopathy

“…These receptors, central to the innate immune system, demonstrate intricate interactions, i.e., TLR-4 in uences the expression or activity of other lipid receptors such as LOX-1 and CD36, thereby impacting cellular lipid uptake. Speci cally, LOX-1 serves as a receptor for Ox-LDL, recognizing and binding it to facilitate cellular uptake, intracellular degradation, and metabolism, thereby reducing extracellular lipid accumulation [29][30]. Concurrently, the synergistic effect between LOX-1 and TLR-4 mutually enhanced their activity [31], while TLR-4 further augmented the uptake of Ox-LDL by macrophages via CD36 upregulation and initiates in ammatory signaling pathways [32].…”

Atorvastatin Decreases Renal Calcium Oxalate Stone Deposits by Enhancing Renal Osteopontin Expression in Hyperoxaluric Stone-Forming Rats Fed a High-Fat Diet

“…OxLDL can cause damage in renal mesangial cells, endothelial cells, and podocytes [ 37 ]. An in vivo study using human glomerular mesangial cells reported oxLDL uptake via LOX-1 accompanied by increased ROS production, further enhancing oxLDL endocytosis [ 38 ]. However, increased severity of renal injury after HFD intake but decreased expression of renal LOX-1 were found in the current study, which is in contrast to the findings in previous reports.…”