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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Published on: June 29, 2011

JNK activation limits dendritic cell maturation in response to reactive oxygen species by the induction of apoptosis

Matthew E Handley1, Manish Thakker, Gabriele Pollara

  • 1Department of Immunology and Molecular Pathology, University College London, Windeyer Institute, 46 Cleveland Street, London W1T 4JF, UK.

Free Radical Biology & Medicine
|May 27, 2005
PubMed

Insights

Hydrogen peroxide (H2O2) activates key immune signaling pathways (MAPK) in dendritic cells (DCs). High H2O2 concentrations induce DC apoptosis via JNK activation, potentially limiting harmful immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Dendritic cells (DCs) are crucial for initiating T cell immunity.
  • Mitogen-activated protein kinase (MAPK) pathways regulate DC responses.
  • Hydrogen peroxide (H2O2), a reactive oxygen species, is present in inflammatory environments and activates MAPK.

Purpose of the Study:

  • To investigate the role of H2O2 in regulating MAPK activation (p38 and JNK), DC phenotype, and apoptosis.
  • To examine the combined effects of H2O2 and lipopolysaccharide (LPS) on these DC functions.

Main Methods:

  • Human monocyte-derived DCs were treated with varying concentrations of H2O2, alone and with LPS.
  • MAPK activation, DC phenotype, and apoptosis were assessed.
  • Specific JNK inhibitors (CEP11004, SP600125) were used to evaluate JNK's role.

Main Results:

  • Low H2O2 concentrations activated p38 MAPK but did not alter DC phenotype.
  • Higher H2O2 concentrations activated both p38 and JNK MAPK.
  • JNK activation correlated with increased DC apoptosis, partially inhibited by JNK inhibitors.
  • H2O2 and LPS synergistically induced JNK activation and DC apoptosis.

Conclusions:

  • H2O2 modulates DC function, with higher concentrations inducing apoptosis via JNK activation.
  • JNK-mediated apoptosis in DCs may serve as a mechanism to prevent excessive immune responses.
  • The synergistic effect of H2O2 and LPS highlights complex inflammatory signaling in DCs.

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