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.

• Authors: Yuanjian Song, Li Qin, Rongli Yang, Fan Yang, Nwobodo Alexander Kenechukwu, Xiaofang Zhao, Xiaoyan Zhou, Xiangru Wen, Lei Li
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 57 Issue 1 Pg. 263-268 (Dec 2019) ISSN: 1744-5116 [Electronic] England
• PMID: 31124385 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Hydroxamic Acids
• Indoles
• Inflammation Mediators
• Lipopolysaccharides
• tubastatin A
• p38 Mitogen-Activated Protein Kinases
• Hdac6 protein, mouse
• Histone Deacetylase 6

Topics

• Animals
• Disease Models, Animal
• Encephalitis (enzymology, prevention & control)
• Enzyme Inhibitors (pharmacology)
• Histone Deacetylase 6 (antagonists & inhibitors)
• Hydroxamic Acids (pharmacology)
• Indoles (pharmacology)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides
• Male
• Mice, Inbred Strains
• Phosphorylation
• p38 Mitogen-Activated Protein Kinases (metabolism)