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HMGB1: LPS Delivery Vehicle for Caspase-11-Mediated Pyroptosis

Ho Min Kim1, You-Me Kim1

  • 1Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.

Immunity
|October 18, 2018
PubMed

Insights

High-mobility group box 1 (HMGB1) secreted by liver cells delivers lipopolysaccharide (LPS) into the cytoplasm, triggering pyroptosis and inflammation. This discovery reveals a new mechanism in inflammatory responses.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Caspase-11 activation by cytoplasmic lipopolysaccharide (LPS) initiates pyroptosis, a pro-inflammatory cell death pathway.
  • Understanding the precise mechanisms of cytoplasmic LPS sensing is crucial for controlling inflammatory diseases.

Purpose of the Study:

  • To elucidate the role of high-mobility group box 1 (HMGB1) in mediating the delivery of extracellular LPS into the hepatocyte cytoplasm.
  • To investigate the downstream consequences of HMGB1-mediated LPS translocation on pyroptosis induction.

Main Methods:

  • Hepatocyte culture and stimulation with LPS.
  • Immunofluorescence and biochemical assays to detect LPS and HMGB1 localization.
  • Caspase-11 activation assays and pyroptosis assessment.

Main Results:

  • Hepatocyte-secreted HMGB1 binds to extracellular LPS.
  • HMGB1 facilitates the internalization of LPS into the hepatocyte cytoplasm.
  • Cytoplasmic LPS triggers caspase-11-dependent pyroptosis.

Conclusions:

  • HMGB1 acts as a critical mediator, delivering extracellular LPS into the cytoplasm of hepatocytes.
  • This HMGB1-LPS interaction triggers pyroptosis, contributing to inflammatory mediator secretion.
  • The findings reveal a novel pathway in LPS-induced inflammation and pyroptosis.

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