Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression

Sorafenib is an anti-tumor drug widely used in clinical treatment, which can inhibit tyrosine kinase receptor on cell surface and serine/threonine kinase in downstream Ras/MAPK cascade signaling pathway of cells. Tyrosine kinase phosphorylation plays an important role in inflammatory mechanism, such...

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Bibliographic Details
Published in:Cell death discovery 2022-06, Vol.8 (1), p.281-281, Article 281
Main Authors: Li, Xiaolian, Xu, Mingkun, Shen, Jiaojiao, Li, Yuqin, Lin, Shaoping, Zhu, Min, Pang, Qiongni, Tan, Xiujuan, Tang, Jing
Format: Article
Language:English
Subjects:
631/250/256/1980
692/699/255/2514
Apoptosis
Biochemistry
Biomedical and Life Sciences
c-Jun protein
Cell Biology
Cell Cycle Analysis
Cell surface
IL-1β
Inflammation
Inhibitor drugs
Interleukin 6
Kinases
Life Sciences
Lipopolysaccharides
Macrophages
MAP kinase
NF-κB protein
Phosphorylation
Protein-serine/threonine kinase
Protein-tyrosine kinase receptors
Sepsis
Signal transduction
Stem Cells
Targeted cancer therapy
TLR4 protein
Toll-like receptors
Transcription factors
Tumor necrosis factor-α
Tumors
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Summary:Sorafenib is an anti-tumor drug widely used in clinical treatment, which can inhibit tyrosine kinase receptor on cell surface and serine/threonine kinase in downstream Ras/MAPK cascade signaling pathway of cells. Tyrosine kinase phosphorylation plays an important role in inflammatory mechanism, such as TLR4 tyrosine phosphorylation, MAPK pathway protein activation, and activation of downstream NF-кB. However, the effects of sorafenib on LPS-induced inflammatory reaction and its specific mechanism have still remained unknown. We found that sorafenib inhibited the phosphorylation of tyrosine kinase Lyn induced by LPS, thereby reducing the phosphorylation level of p38 and JNK, inhibiting the activation of c-Jun and NF-κB, and then inhibiting the expression of inflammatory factors IL-6, IL-1β, and TNF-α. Furthermore, sorafenib also decreased the expression of TLR4 on the macrophage membrane to inhibit the expression of inflammatory factors latterly, which may be related to the inactivation of Lyn. These results provide a new perspective and direction for the clinical treatment of sepsis.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-022-01073-7