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Trichostatin A inhibits dendritic cell maturation through down-regulating NF—κ B (p65) pathway

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Abstract

Background

Recent evidence suggested that histone deacetylase inhibitor (HDACi) could inhibit dendritic cell (DC) maturation. However, the mechanism is unclear. Here, we aimed to study whether Trichostatin A (TSA), the most widely studied HDACi, inhibits the maturation of DCs by down-regulating NF-κB (p65) pathway.

Methods and results

Mouse bone marrow-derived DCs were cultured. Lipopolysaccharide (LPS) was applied as stimulation for maturation. Triptolide (TTL) was applied as p65 inhibitor. Microphotography and flow cytometry showed that TSA and p65 inhibitor separately inhibited the maturation of DCs stimulated by LPS from the aspects of cell morphology and cell phenotype. Mixed lymphocyte reaction test and ELISA showed that TSA and p65 inhibitor synergistically inhibited the proliferation of T lymphocytes stimulated by DCs, reduced the secretion of pro-inflammatory cytokine IL-12 and elevated the secretion of anti-inflammatory cytokine IL-10. Western blot and RT-qPCR showed that TSA down-regulated the expression of phosphorylated IκBα, phosphorylated-p65, Ikkβ and Ikkγ, suggesting TSA down-regulates NF-κB (p65) pathway.

Conclusions

TSA inhibits DC maturation through down-regulating NF-κB (p65) pathway.

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Data Availability

The experiment data used to support the findings of this study are included within the article.

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Acknowledgements

We appreciate all the coworkers who participated in this study.

Funding

This study is supported by the Basic and Applied Research Programs of Guangzhou Science and Technology Plan Project, China (No. 202102020929), also by the Guangdong Province Science and Technology Major Plan Project, China (No. 2014B020212019). The funders have no role in study design; collection, management, analysis, or interpretation of data; writing of the report; or the decision to submit the report for publication.

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Authors and Affiliations

  1. Department of Ophthalmology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No.9 Jinsui Road, Guangzhou, 510623, China

    Ying Yu, Bing Liu, Siyan Chen, Jianxun Wang, Feng Chen, Tian Liu, Nan Jiang, Wensi Chen, Shengbei Weng, Xiaoxiao Cai & Daoman Xiang

Authors
  1. Ying Yu
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  2. Bing Liu
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  6. Tian Liu
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Contributions

YY and DX conceptualized and designed the study. BL, SC, NJ, and WC performed experiments. SW and XC analyzed data. YY drafted the initial manuscript. DX, JW, FC, and TL reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Daoman Xiang.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

The authors declare that no in vivo animal experiments or human participants were included in this study. The cells in our experiments were obtained directly from the animals. Our study was approved by the Institutional Review Board- Ethics Committee of Guangzhou Women and Children’s Medical Center, Guangzhou Medical University. All procedures were conducted in accordance with the Guiding Principles in the Care and Use of Animals (China).

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Ying Yu, Bing Liu and Siyan Chen share the first authorship.

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Yu, Y., Liu, B., Chen, S. et al. Trichostatin A inhibits dendritic cell maturation through down-regulating NF—κ B (p65) pathway. Mol Biol Rep 49, 2619–2627 (2022). https://doi.org/10.1007/s11033-021-07065-7

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  • DOI: https://doi.org/10.1007/s11033-021-07065-7

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