HAT inhibitor, garcinol, exacerbates lipopolysaccharide‑induced inflammation in vitro and in vivo

Wang,Bin; Lin,Ling; Ai,Qing; Zeng,Tao; Ge,Pu; Zhang,Li

doi:10.3892/mmr.2016.5189

HAT inhibitor, garcinol, exacerbates lipopolysaccharide‑induced inflammation in vitro and in vivo

Authors:
- Bin Wang
- Ling Lin
- Qing Ai
- Tao Zeng
- Pu Ge
- Li Zhang
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Physiology, Chongqing Medical University, Chongqing 400016, P.R. China, Medical College, Jingchu University of Technology, Jingmen, Hubei 448000, P.R. China
Published online on: April 26, 2016 https://doi.org/10.3892/mmr.2016.5189
Pages: 5290-5296

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Abstract

Acetylation modification catalyzed by histone acetyl transferases (HATs) is important for transcriptional regulation. The present study investigated the effects of the HAT inhibitor garcinol on the expression of inflammation‑associated genes in lipopolysaccharide (LPS)‑stimulated RAW264.7 murine macrophages and LPS‑challenged mice. The levels of pro‑inflammatory cytokines were determined by reverse transcription‑quantitative polymerase chain reaction and enzyme‑linked immunosorbent assay. The degree of multi‑organ injury was evaluated by histopathological examination of the lung, determination of the alanine aminotransferase and blood urea nitrogen in plasma samples and by monitoring the survival rate of the experimental animals. The results of the current study demonstrated that garcinol promoted LPS‑induced expression of tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) in RAW264.7 cells. These effects were associated with reduced acetylation of nuclear factor‑κB p65. Additionally, treatment with garcinol enhanced LPS‑induced expression of TNF‑α and IL‑6, exacerbated LPS‑induced lung injury, increased LPS‑induced elevation of plasma alanine aminotransferase and blood urea nitrogen, and reduced the survival rate of LPS‑challenged mice. These data indicated that the HAT inhibitor, garcinol, enhances LPS‑induced inflammation in vitro and in vivo, suggesting that acetylation modification has an important regulatory function during inflammation.

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