MLN4924 suppresses lipopolysaccharide‑induced proinflammatory cytokine production in neutrophils in a dose‑dependent manner

  • Authors:
    • Jiayang Jin
    • Zhaofei Jing
    • Zhenjie Ye
    • Lu Guo
    • Lei Hua
    • Qingyang Wang
    • Jing Wang
    • Qianqian Cheng
    • Jiyan Zhang
    • Yunlu Xu
    • Lin Wei
  • View Affiliations

  • Published online on: March 23, 2018     https://doi.org/10.3892/ol.2018.8333
  • Pages: 8039-8045
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Abstract

Neddylation is a ubiquitination‑like pathway. It has been reported that neddylation inhibition with the pharmacological agent MLN4924 potently uppresses lipopolysaccharide (LPS)‑induced proinflammatory cytokine production, including tumor necrosis factor (TNF)‑α and interleukin (IL)‑6, by preventing the degradation of phosphorylated inhibitor of κB (p‑IκB) in macrophages. However, whether neddylation serves a similar role in neutrophils remains unknown. In the present study MLN4924 treatment led to the accumulation of P‑IκBα in neutrophils as well as the decreased production of TNF‑α, IL‑6 and IL‑1β in response to LPS, in a dose‑dependent manner. The viability of neutrophils was only marginally affected in the same conditions, without statistical significance. Furthermore, the nuclear factor (NF)‑κB inhibitor JSH‑23 mimicked the effects of MLN4924 in neutrophils, and the inhibitory effects of MLN4924 on LPS‑induced proinflammatory cytokine production diminished in the presence of JSH‑23. Thus, the results of the present study suggest that neddylation inhibition suppresses neutrophil function by suppressing the NF‑κB signaling pathway.
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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Jin J, Jing Z, Ye Z, Guo L, Hua L, Wang Q, Wang J, Cheng Q, Zhang J, Xu Y, Xu Y, et al: MLN4924 suppresses lipopolysaccharide‑induced proinflammatory cytokine production in neutrophils in a dose‑dependent manner. Oncol Lett 15: 8039-8045, 2018
APA
Jin, J., Jing, Z., Ye, Z., Guo, L., Hua, L., Wang, Q. ... Wei, L. (2018). MLN4924 suppresses lipopolysaccharide‑induced proinflammatory cytokine production in neutrophils in a dose‑dependent manner. Oncology Letters, 15, 8039-8045. https://doi.org/10.3892/ol.2018.8333
MLA
Jin, J., Jing, Z., Ye, Z., Guo, L., Hua, L., Wang, Q., Wang, J., Cheng, Q., Zhang, J., Xu, Y., Wei, L."MLN4924 suppresses lipopolysaccharide‑induced proinflammatory cytokine production in neutrophils in a dose‑dependent manner". Oncology Letters 15.5 (2018): 8039-8045.
Chicago
Jin, J., Jing, Z., Ye, Z., Guo, L., Hua, L., Wang, Q., Wang, J., Cheng, Q., Zhang, J., Xu, Y., Wei, L."MLN4924 suppresses lipopolysaccharide‑induced proinflammatory cytokine production in neutrophils in a dose‑dependent manner". Oncology Letters 15, no. 5 (2018): 8039-8045. https://doi.org/10.3892/ol.2018.8333