Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 56, Issue -, Pages 230-234Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2018.01.039
Keywords
HDAC6; Tubastatin; ROS; Inflammation; Cytokines; NF-kappa B
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Funding
- National Science Foundation of China [31602122, 31572583]
- China Postdoctoral Science Foundation [2016M600233]
- Graduate Innovation Fund of Jilin University project [2017167]
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Histone deacetylase 6 (HDAC6) is the sole member of the HDAC family, that is predominantly located in the cytoplasm and has substrate specificity for nonhistone proteins, such as alpha-Tubulin. Although an increasing number of studies have shown that HDAC6 is involved in inflammatory diseases, but little is known about the participation of HDAC6 in the transcriptional regulation of inflammatory cytokines. Here, we examined the effects of Tubastatin (Tub), a highly selective HDAC6 inhibitor, on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMECs). The specific inhibition of HDAC6 using Tub significantly decreased the release of pro-inflammatory cytokines, such as TNF-alpha and IL-1 beta, which was associated with increased alpha-Tubulin acetylation. HDAC6 overexpression significantly induced reactive oxygen species (ROS) generation via upregulation of NADPH oxidase activity. Administration of Tub dose-dependently inhibited ROS production and NADPH oxidase activity. In addition, inhibition of HDAC6 led to suppression of the NF-kappa B signaling pathway. Thus, we report herein that HDAC6 is involved in ROS-NF-kappa B signaling pathway related to pro-inflammatory cytokine expression and that selective HDAC6 inhibition by Tub is a potent approach for preventing LPS-mediated inflammation.
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