Sorafenib Inhibits LPS-induced Inflammation by Regulating Lyn-MAPK-NF-kB/AP-1 Pathway and TLR4 Expression

Overview

Journal Cell Death Discov

Date 2022 Jun 10

PMID 35680841

Authors

Xiaolian Li

Mingkun Xu

Jiaojiao Shen

Yuqin Li

Shaoping Lin

Min Zhu

Qiongni Pang

Xiujuan Tan

Jing Tang

Affiliations

Soon will be listed here.

Abstract

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.

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