Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF‑κB pathway

  • Authors:
    • Yuan Yu
    • Ling Zhang
    • Qi Liu
    • Lin Tang
    • Hang Sun
    • Hui Guo
  • View Affiliations

  • Published online on: November 17, 2014     https://doi.org/10.3892/mmr.2014.2960
  • Pages: 2048-2054
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Abstract

Elevated plasma low‑density lipoprotein (LDL) is associated with systemic inflammation, and is an important factor in the pathogenesis of chronic kidney disease. The aim of the present study was to investigate the effects of endoplasmic reticulum (ER) stress preconditioning on LDL‑induced inflammatory responses, in human mesangial cells (HMCs). HMCs were exposed to LDL (200 nm), with or without pretreatment with tunicamycin, an ER stress inducer, and tested for changes to gene expression levels. Small interfering RNA technology was used to knockdown the expression of inositol‑requiring enzyme‑1α (IRE1α) and X‑box‑binding protein‑1 (XBP‑1), in order to determine their effects on LDL‑treated HMCs. LDL treatment resulted in a significant, and time‑dependent, increase in the relative mRNA expression levels of proinflammatory cytokines and CD40, which was coupled with enhanced phosphorylation of IRE1α, IκB kinase (IKK), and nuclear factor (NF)‑κB p65 and p65 nuclear translocation. The LDL‑induced inflammatory responses were significantly reduced in the IRE1α‑depleted HMCs. Furthermore, pretreatment with tunicamycin significantly attenuated the induction of proinflammatory cytokines and CD40, by LDL. Whereas, silencing XBP1 expression significantly restored the production of proinflammatory cytokines, in the LDL‑treated HMCs with ER stress preconditioning. The phosphorylation levels of IRE1α, IKK, and NF‑κB p65 were markedly increased in the XBP1‑depleted HMCs. Conversely, overexpression of XBP1 blocked LDL‑induced inflammation in the HMCs. The results of the present study demonstrate that ER stress preconditioning antagonizes LDL‑induced inflammatory responses in HMCs, which may be mediated through upregulation of XBP1, and subsequent inactivation of the IRE1α/IKK/NF‑κB pathway.
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March-2015
Volume 11 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yu Y, Zhang L, Liu Q, Tang L, Sun H and Guo H: Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF‑κB pathway. Mol Med Rep 11: 2048-2054, 2015.
APA
Yu, Y., Zhang, L., Liu, Q., Tang, L., Sun, H., & Guo, H. (2015). Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF‑κB pathway. Molecular Medicine Reports, 11, 2048-2054. https://doi.org/10.3892/mmr.2014.2960
MLA
Yu, Y., Zhang, L., Liu, Q., Tang, L., Sun, H., Guo, H."Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF‑κB pathway". Molecular Medicine Reports 11.3 (2015): 2048-2054.
Chicago
Yu, Y., Zhang, L., Liu, Q., Tang, L., Sun, H., Guo, H."Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF‑κB pathway". Molecular Medicine Reports 11, no. 3 (2015): 2048-2054. https://doi.org/10.3892/mmr.2014.2960