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SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
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Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression

Xiaolian Li1, Mingkun Xu1, Jiaojiao Shen1

  • 1Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, 524000, Zhanjiang City, Guangdong Province, China.

Cell Death Discovery
|June 10, 2022
PubMed

Insights

Sorafenib effectively reduces inflammation by inhibiting key signaling pathways like Lyn tyrosine kinase and Toll-like receptor 4 (TLR4). This drug offers a new therapeutic strategy for sepsis treatment.

Area of Science:

  • Pharmacology
  • Immunology
  • Molecular Biology

Background:

  • Sorafenib is an anti-tumor drug targeting tyrosine and serine/threonine kinases.
  • Tyrosine kinase phosphorylation is crucial in inflammatory processes, involving TLR4, MAPK, and NF-κB pathways.
  • The effect of sorafenib on lipopolysaccharide (LPS)-induced inflammation remains unclear.

Purpose of the Study:

  • To investigate the effects of sorafenib on LPS-induced inflammatory reactions.
  • To elucidate the specific molecular mechanisms underlying sorafenib's anti-inflammatory actions.

Main Methods:

  • Assessing sorafenib's impact on Lyn tyrosine kinase phosphorylation induced by LPS.
  • Analyzing the phosphorylation levels of p38 and JNK.
  • Evaluating the activation of c-Jun and NF-κB.
  • Measuring the expression of inflammatory factors (IL-6, IL-1β, TNF-α) and TLR4 on macrophages.

Main Results:

  • Sorafenib inhibited LPS-induced Lyn tyrosine kinase phosphorylation.
  • This inhibition led to reduced phosphorylation of p38 and JNK, and suppressed c-Jun and NF-κB activation.
  • Sorafenib decreased the expression of inflammatory factors IL-6, IL-1β, and TNF-α.
  • Sorafenib also reduced TLR4 expression on macrophages, potentially via Lyn inactivation.

Conclusions:

  • Sorafenib demonstrates significant anti-inflammatory effects by modulating the Lyn/TLR4 signaling pathway.
  • These findings suggest sorafenib as a potential therapeutic agent for sepsis and other inflammatory conditions.

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