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01-12-2019 | Septicemia | Original Article

Inhibition of Fibroblast Growth Factor Receptor by AZD4547 Protects Against Inflammation in Septic Mice

Authors: Yueyue Huang, Fen Wang, Hao Li, ShunYao Xu, Wenwei Xu, XiaoJun Pan, Yufeng Hu, Lingjie Mao, Songzan Qian, Jingye Pan

Published in: Inflammation | Issue 6/2019

Abstract

Sepsis is a life-threatening condition caused by the dysregulated host immune response to infection characterized by excessive secretion of inflammatory factors. AZD4547 is a selective inhibitor of fibroblast growth factor receptors that participates in the inflammatory response. The aim of this study was to investigate the inflammation-targeting effects and related molecular mechanisms of AZD4547 in sepsis using a cecal ligation and puncture model and RAW264.7 macrophages stimulated with lipopolysaccharide. AZD4547 improved the survival of CLP mice and exhibited a robust protective function against lung damage histologically. Pretreatment with AZD4547 significantly alleviated the expression of the pro-inflammatory factors IL-1β, IL-6, TNF-α, MMP9, and CXCL10 both in vivo and in vitro. In addition, AZD4547 suppressed the proliferative activity of macrophages in lung tissue and RAW264.7 macrophages. In addition, the LPS-induced phosphorylation of key proteins of NF-κB/MAPK/STAT3 pathways in RAW264.7 macrophages, such as p65, IκB-α, Erk1/2, JNK, and STAT3 proteins, could be inhibited by AZD4547 pretreatment. In conclusion, AZD4547 exerts a protective effect against excessive inflammatory damage in septic mice and may have the potential for use as an effective drug for the management of sepsis.

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Title: Inhibition of Fibroblast Growth Factor Receptor by AZD4547 Protects Against Inflammation in Septic Mice
Authors: Yueyue Huang
Fen Wang
Hao Li
ShunYao Xu
Wenwei Xu
XiaoJun Pan
Yufeng Hu
Lingjie Mao
Songzan Qian
Jingye Pan
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Septicemia
Septicemia
Cytokines
Published in: Inflammation / Issue 6/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-019-01056-4

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