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Interleukin-1β enhances the intracellular accumulation of cholesterol by up-regulating the expression of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in podocytes

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Abstract

The aim of this article is to investigate whether interleukin-1β (IL-1β) could regulate the intracellular accumulation of cholesterol and the expression of lipid-metabolism-related regulators in podocytes in vitro and the potential mechanisms. Podocytes were treated with 200 μg/ml of low-density protein (LDL), 20 ng/ml of IL-1β, or 200 μg/ml of LDL plus 5–20 ng/ml of IL-1β for 24 h in vitro. The contents of intracellular cholesterol were determined by enzymatic assays and Oil Red O staining. The levels of LDL receptor (LDLr), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, sterol regulatory element binding protein 2 (SREBP-2), SREBP cleavage activating protein (SCAP), and insulin-induced gene-1 (Insig-1) expression were characterized by real-time polymerase chain reaction (RT-PCR) and Western blot assays. Treatment with IL-1β or LDL alone increased the contents of intracellular cholesterol (P < 0.05 for both) and lipid droplets, and treatment with both IL-1β and LDL further increased the accumulation of intracellular cholesterol in podocytes (P < 0.05 vs. LDL alone). While loading with LDL significantly inhibited the expression of LDLr, HMG-CoA reductase, nuclear SREBP-2 (nSREBP-2), SCAP, and Insig-1 by 40–62% treatment with IL-1β enhanced the expression of LDLr, HMG-CoA reductase and nSREBP-2, but not Insig-1, in podocytes (P < 0.05 vs. control). Treatment with both LDL and IL-1β significantly increased the levels of LDLr and HMG-CoA reductase expression and the ratio of SCAP to Insig-1, as compared with that in the LDL-treated podocytes (P < 0.05 vs. LDL alone). Our data indicated that IL-1β mitigated the LDL-triggered SCAP-SREBP-2-mediated feedback inhibition on the expression of LDLr and HMG-CoA reductase, leading to the intracellular accumulation of LDL-cholesterol in podocytes in vitro.

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Acknowledgments

We would like to thank Dr. Xiong Z Ruan (Renal Research Unit, Department of Nephrology, Royal Free Hospital School of Medicine, London, UK) for his generous provision of key reagents, technical assistance, and critical comments. This study was financially supported by the grants from the National Natural Science Foundation of China (grant no. 30672267) and Natural Science Foundation Project of CQ CSTC (grant no. CSTC, 2009BA5080).

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Authors and Affiliations

  1. Department of Nephroimmunology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of China

    Gaofu Zhang, Qiu Li, Li Wang, Lijia Wang & Wei Zhang

  2. Centre for Lipid Research, Chongqing Medical University, Chongqing, People’s Republic of China

    Gaofu Zhang, Qiu Li & Yaxi Chen

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  1. Gaofu Zhang
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  2. Qiu Li
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Correspondence to Qiu Li.

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Zhang, G., Li, Q., Wang, L. et al. Interleukin-1β enhances the intracellular accumulation of cholesterol by up-regulating the expression of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in podocytes. Mol Cell Biochem 346, 197–204 (2011). https://doi.org/10.1007/s11010-010-0605-4

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  • DOI: https://doi.org/10.1007/s11010-010-0605-4

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