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The Attenuation of 14-3-3ζ is Involved in the Caffeic Acid-Blocked Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages

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Abstract

Inflammation plays important roles in the initiation and progress of many diseases. Caffeic acid (CaA) is a naturally occurring hydroxycinnamic acid derivative, which shows hypotoxicity and diverse biological functions, including anti-inflammation. The molecular mechanisms involved in the CaA-inhibited inflammatory response are very complex; generally, the down-regulated phosphorylation of such important transcriptional factors, for example, nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT-3), plays an important role. Here, we found that in RAW264.7 macrophage cells, CaA blocked lipopolysaccharide (LPS)-stimulated inflammatory response by attenuating the expression of 14-3-3ζ (a phosphorylated protein regulator). Briefly, the increased expression of 14-3-3ζ was involved in the LPS-induced inflammatory response. CaA blocked the LPS-elevated 14-3-3ζ via attenuating the LPS-induced tumor necrosis factor-α (TNF-α) secretion and via enhancing the 14-3-3ζ ubiquitination. These processes inhibited the LPS-induced activation (phosphorylation) of NF-κB and STAT-3, in turn blocked the transcriptional activation of inducible NO synthase (iNOS), interleukin-6 (IL-6), and TNF-α, and finally attenuated the productions of nitric oxide (NO), IL-6, and TNF-α. By understanding a novel mechanism whereby CaA inhibited the 14-3-3ζ, our study expanded the understanding of the molecular mechanisms involved in the anti-inflammation potential induced by CaA.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81602841 to Ye Yang and 81572325 to Jianping Zhang) and the Technology Development Fund of Nanjing Medical University (2014NJMU002 to Ye Yang and HL201417 to Zhiping Chu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Ming Lu, Yi Dai, and Miao Xu contributed equally to this work.

Authors and Affiliations

  1. The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, China

    Ming Lu, Yi Dai, Chi Zhang, Yuhong Ma, Ping Gao, Guangming Huang, Jianping Zhang & Zhiping Chu

  2. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Miao Xu, Mengying Teng, Kailin Jiao & Ye Yang

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  1. Ming Lu
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Lu, M., Dai, Y., Xu, M. et al. The Attenuation of 14-3-3ζ is Involved in the Caffeic Acid-Blocked Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages. Inflammation 40, 1753–1760 (2017). https://doi.org/10.1007/s10753-017-0618-1

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