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A NF-κB-Based High-Throughput Screening for Immune Adjuvants and Inhibitors

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Abstract

The nuclear factor-κB (NF-κB) family is crucial for regulating immune and inflammatory responses. The activation of the immune cell signaling pathway usually activates NF-κB, causing a protective immune response. NF-κB can also cause excessive inflammatory responses by activating a cascade reaction of pro-inflammatory mediators such as cytokines. In this study, we used an NF-κB luciferase reporter gene system. Out of more than 800 compounds screened, four NF-κB agonists were identified with strong activity at nontoxic concentrations. Subsequently, the adjuvant effect was verified on mouse bone marrow-derived dendritic cells (BMDCs) and macrophages RAW264.7. It was found that fostamatinib (R788) disodium increased the production of IL-6, IL-12p40, and TNF-α, indicating that R788 disodium could induce the maturation of antigen-presenting cells (APCs). In addition, three compounds were screened to significantly inhibit NF-κB at nontoxic doses, including dehydrocostus lactone (DHL)–a known NF-κB inhibitor. The results showed that DHL significantly reduced the release of LPS-induced inflammatory cytokines (including TNF-α, IL-6, and IL-12). Our findings indicate that the NF-κB-based high-throughput screening can be used to discover potential immune adjuvants and anti-inflammatory molecules.

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Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dr. Yaran Chang and Dr. Wenmei Zhang from Beijing University of Technology for assistance with the experiments.

Funding

This research was funded by the National Key Research and Development Program of China, grant number (2018YFC1708105, 2018YFC1708100) and the National Natural Science Foundation of China, grant number (81760783).

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Authors and Affiliations

  1. The Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, China

    Boyang Yu, Tian Chen, Jinning Yang, Xiaoli Wang & Qin Hu

  2. Beijing International Science and Technology Cooperation Base of Antivirus Drug, Beijing University of Technology, Beijing, 100124, China

    Boyang Yu, Tian Chen, Jinning Yang, Xiaoli Wang & Qin Hu

  3. Civil Aviation Medicine Center, Civil Aviation Administration of China, Beijing, 100123, China

    Boye Li

  4. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Bo Peng

Authors
  1. Boyang Yu
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  2. Boye Li
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  3. Tian Chen
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  4. Jinning Yang
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  5. Xiaoli Wang
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  6. Bo Peng
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Contributions

All authors contributed to the study conception and design. Conceived and designed the experiments: Qin Hu, Boyang Yu, and Boye Li. Performed the experiments: Boyang Yu, Tian Chen, and Bo Peng. Analyzed the data: Tian Chen and Jinning Yang. Provision of instrumentation: Xiaoli Wang. Prepared the manuscript: Qin Hu and Boyang Yu. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Bo Peng or Qin Hu.

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Experiments were approved by the Institutional Animal Treatment and Use Committee, China Academy of Chinese Medica Sciences (code: 2021B218).

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Yu, B., Li, B., Chen, T. et al. A NF-κB-Based High-Throughput Screening for Immune Adjuvants and Inhibitors. Inflammation 46, 598–611 (2023). https://doi.org/10.1007/s10753-022-01758-2

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  • DOI: https://doi.org/10.1007/s10753-022-01758-2

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