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TWEAK promotes inflammatory response in liver fibrosis

Yun Kong1, Yi Yang1, Shasha Wu1

  • 1Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

Journal of Biochemical and Molecular Toxicology
|July 28, 2023
PubMed

Insights

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes M1 polarization in liver cells, contributing to liver fibrosis. Inhibiting NLRP3 or CD266 can mitigate TWEAK

Area of Science:

  • Immunology
  • Hepatology
  • Cell Biology

Background:

  • Liver fibrosis is a significant health concern.
  • Kupffer cells (KCs) play a crucial role in liver inflammation and fibrosis.
  • Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the role of TWEAK in liver fibrosis.
  • To elucidate the mechanism by which TWEAK influences M1 polarization of liver macrophages.
  • To evaluate TWEAK's impact on a mouse model of liver fibrosis.

Main Methods:

  • Primary liver Kupffer cells (KCs) and J774A.1 macrophages were cultured and induced for M1 polarization.
  • TWEAK was administered, followed by analysis of M1 cell proportion and cytokine levels.
  • CD266 expression was silenced, and NLRP3 inflammasome was inhibited to assess their role.
  • A mouse model of liver fibrosis was established to evaluate TWEAK's in vivo effects.

Main Results:

  • TWEAK significantly promoted M1 polarization of KCs and J774A.1 cells.
  • Silencing CD266 or inhibiting NLRP3 suppressed TWEAK-induced M1 polarization.
  • In vivo studies showed that TWEAK exacerbated liver fibrosis, while NLRP3 inhibition improved liver function and reduced M1 cell levels.

Conclusions:

  • TWEAK drives liver fibrosis by promoting M1 macrophage polarization.
  • The TWEAK-mediated M1 polarization involves CD266 and the NLRP3 inflammasome.
  • Targeting NLRP3 offers a potential therapeutic strategy to counteract TWEAK-induced liver fibrosis.
Keywords:
Kupffer cellsM1 polarizationTWEAKinflammationliver fibrosis

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