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ZEB2 Attenuates LPS-Induced Inflammation by the NF-κB Pathway in HK-2 Cells

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Abstract

As a transcription factor, zinc finger E-box binding homeobox 2 (ZEB2) includes multiple functional domains which interact with kinds of transcriptional co-effectors. It has been reported that ZEB2 was involved in signal transduction and multiple cellular functions. However, the functional role of ZEB2 in inflammation is still obscure. The aim of the current study is to explore the function of ZEB2 in inflammation cytokine secretion and the role of the nuclear factor-κB (NF-κB) signaling pathway in lipopolysaccharide (LPS)-induced human proximal tubule cell line (HK-2) cells. Our result demonstrated that expression of ZEB2 was significantly downregulated and expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was upregulated in response to LPS. Meanwhile, knockdown of ZEB2 by transfecting siRNA increased TNF-α and IL-6 secretion. Overexpression of ZEB2 resulted in a decrease of TNF-α and IL-6 secretion in HK-2 cells. Additionally, Western blot analysis indicated that ZEB2 suppressed the activation of the NF-κB signaling pathway via downregulating the levels of phosphorylated p65 and IκBα compared with LPS stimulation. Collectively, our data demonstrated that ZEB2 attenuated LPS-induced inflammation cytokine secretion possibly through suppressing the NF-κB signaling pathway.

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Abbreviations

AKI:

Acute kidney injury

DMEM:

Dulbecco’s modified Eagle’s medium

EMT:

Epithelial-mesenchymal transition

HK-2 cell:

Human kidney epithelial cell

IL-6:

Interleukin-6

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor-κB

PCR:

Polymerase chain reaction

p-p65:

Phosphorylated p65

p-IκBα:

Phosphorylated IκBα

PDTC:

Pyrrolidine dithiocarbamate

siRNA:

Small interfering RNA

TGF-β1:

Transforming growth factor beta 1

TNF-α:

Tumor necrosis factor-α

ZEB2:

Zinc finger E-box-binding homeobox 2

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Acknowledgements

This study was supported by the Chinese National Natural Science Foundation Project (81100302) and the Intercollegiate Key Projects of Nature Science of Anhui Province (KJ2017A169).

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, 230032, China

    Qi Ding, Yang Wang, Ai-ling Zhang, Tao Xu, Dan-dan Zhou, Xiao-Feng Li, Jun-Fa Yang & Lei Zhang

  2. Key Laboratory of Major Autoimmune Disease, Anhui Province; School of Pharmacy, Anhui Medical University, Hefei, 230032, China

    Qi Ding, Yang Wang, Ai-ling Zhang, Tao Xu, Dan-dan Zhou, Xiao-Feng Li, Jun-Fa Yang & Lei Zhang

  3. The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Anhui Medical University, Hefei, 230032, China

    Qi Ding, Yang Wang, Ai-ling Zhang, Tao Xu, Dan-dan Zhou, Xiao-Feng Li, Jun-Fa Yang & Lei Zhang

  4. Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Ji Xi Road, Hefei, 230022, China

    Xiao Wang

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  1. Qi Ding
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  2. Yang Wang
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Correspondence to Lei Zhang or Xiao Wang.

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Ding, Q., Wang, Y., Zhang, Al. et al. ZEB2 Attenuates LPS-Induced Inflammation by the NF-κB Pathway in HK-2 Cells. Inflammation 41, 722–731 (2018). https://doi.org/10.1007/s10753-017-0727-x

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  • DOI: https://doi.org/10.1007/s10753-017-0727-x

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