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Sodium Butyrate Ameliorates Atopic Dermatitis-Induced Inflammation by Inhibiting HDAC3-Mediated STAT1 and NF-κB Pathway

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Abstract

A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid breakdown by the gut microbiota, have been widely reported in numerous inflammatory diseases. However, the effect of NaB treatment alone on AD has not been reported. In the current study, AD was induced in BALB/c mice with 2,4-dinitrochlorobenzene (DNCB) for 28 days with NaB (200 mg/kg) treatment by gavage. NaB attenuated AD-induced skin bleeding, scarring, dryness, abrasions and erosions. In addition, NaB inhibited inflammatory cells infiltration and attenuated the expression of inflammatory cytokines and chemokines. Mechanistically, NaB reduced histone deacetylase 3 (HDAC3) expression and NF-κB p65 nuclear translocation by increasing the lysine acetylation levels of STAT1 and NF-κB p65 in AD. Taken together, our study suggests that NaB inhibits inflammatory mediators and ameliorates AD by inhibiting HDAC3 expression, thereby upregulating STAT1 and NF-κB p65 lysine acetylation levels and reducing NF-κB p65 nuclear translocation. Therefore, this study provides a new theoretical basis for NaB in the treatment of AD.

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Funding

This study was funded by the Natural Science Foundation of Chongqing, China (No. cstc2020jcyj-bshX0110), and the Foundation of Medical Science and Technology Innovation of Chongqing general hospital, China (No. 2019ZDXM02).

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Authors and Affiliations

  1. Department of Gastroenterology, Chongqing General Hospital, Chongqing, 400014, China

    Chaoqun Hu & Qian Deng

  2. Department of Allergy, Chongqing General Hospital, Chongqing, 400014, China

    Dan Zeng, Weikang Zhou & Wei Zhou

  3. Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Yunxia Huang & Shunan Liu

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  1. Chaoqun Hu
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Contributions

Conceptualization: Wei Zhou, Dan Zeng; Methodology: Chaoqun Hu, Yunxia Huang, Shunan Liu; Validation: Wei Zhou, Chaoqun Hu, Qian Deng; Formal analysis: Wei Zhou, Chaoqun Hu, Qian Deng; Writing-Original Draft: Wei Zhou; Writing-Review & Editing: Chaoqun Hu, Weikang Zhou, Dan Zeng; Funding acquisition: Wei Zhou. All authors have read and agreed to the final version of the manuscript.

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Correspondence to Wei Zhou.

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10753_2023_1955_MOESM1_ESM.tif

Supplementary Figure 1. A No obvious effect of NaB on cell viability of HaCaT cells, indicated by CCK-8 assay (Veh: vehicle, NaB: Sodium Butyrate, n = 6). B NaB preserved the viability of TNF-α/IFN-γ-treated HaCaT cells in a dose-dependent manner, reflected by CCK-8 assay (n = 6, *P < 0.05 vs Control group, #P < 0.05 vs TNF-α/IFN-γ (10 ng/mL) group) (TIF 929 KB)

Supplementary file2 (XLSX 9 KB)

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Hu, C., Zeng, D., Huang, Y. et al. Sodium Butyrate Ameliorates Atopic Dermatitis-Induced Inflammation by Inhibiting HDAC3-Mediated STAT1 and NF-κB Pathway. Inflammation (2023). https://doi.org/10.1007/s10753-023-01955-7

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