Inhibition of HDAC6 alleviating lipopolysaccharide-induced p38MAPK phosphorylation and neuroinflammation in mice

Abstract

Context: Researchers in a variety of fields have extensively focused on histone deacetylase 6 (HDAC6) due to its aggravation of inflammatory reaction. However, relevant studies examining whether HDAC6 could exacerbate lipopolysaccharide (LPS)-induced inflammation are still lacking.

Objective: We assessed the role of HDAC6 in LPS-induced brain inflammation and used the HDAC6-selective inhibitor Tubastatin A (TBSA) to investigate the potential mechanisms further.

Materials and methods: Brain inflammation was induced in Kunming (KM) mice via intraperitoneal (I.P.), injection of Lipopolysaccharide (LPS) (1 mg/kg), the TBSA (0.5 mg/kg) was delivered via intraperitoneal. The phosphorylated p38 (p-p38) Mitogen-activated protein kinases (MAPK) and expression of typical inflammatory mediators, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in both the hippocampus and cortex, were examined by immunoblotting. Nissl staining was used to detect the neuronal damage in the hippocampus and the cortex.

Results: About 1 mg/kg LPS via daily intraperitoneal (I.P.) injections for 12 days significantly increased p38 MAPK phosphorylation, TNF-α and IL-6 expression, and neuronal loss. However, 0.5 mg/kg TBSA (three days before LPS treatment) by I.P. injections for 15 days could reverse the above results.

Conclusions: This present study provided evidence that TBSA significantly suppressed LPS-induced neuroinflammation and the expression of p-p38. Results derived from our study might help reveal the effective targeting strategies of LPS-induced brain inflammation through inhibiting HDAC6.

Keywords:

• Histone deacetylase 6
• Tubastatin A
• inflammation
• phosphorylated p38MAPK

Acknowledgments

We are grateful to Hong-yan Dong, Ting Li, Hong-Hua Yuan, Hong-li Yu, Meng Wang, Bao-le Zhang and Xue-bin Qu in the Research Facility Center for Morphology for providing support and assistance during the experiments.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a grant from the National Natural Science Foundation of China [81671208, 81701298], the Natural Science Foundation of Jiangsu Province [Grants No BK20171180].