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Pharm Biol. 2019 Dec;57(1):263-268. doi: 10.1080/13880209.2018.1563620.

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

Song Y1,2,3, Qin L3, Yang R3, Yang F1,2, Kenechukwu NA1,2, Zhao X1, Zhou X4, Wen X2, Li L1,2,3.

Author information

1
a Department of Genetics , Xuzhou Medical University , Xuzhou , Jiangsu , PR China.
2
b Jiangsu Key Laboratory of Brain Disease Bioinformation , Xuzhou Medical University , Xuzhou , Jiangsu , PR China.
3
c Department of Geriatrics , Affiliated Hospital of Xuzhou Medical University , Xuzhou , Jiangsu , PR China.
4
d Laboratory of Morphology , Xuzhou Medical University , Xuzhou , Jiangsu , PR China.

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

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