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RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages

Zhenyu Yao1, Peng Zhang2, Hui Guo2

  • 1National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Institute of Biomedical and Health Engineering Shenzhen Institutes of Advanced Technology, CAS, China.

Molecular Oncology
|January 14, 2015
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis and autophagy in macrophages. Inhibiting autophagy enhances TRAIL-induced apoptosis, revealing autophagy

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Macrophages are key immune cells regulating pathogen defense and innate immunity.
  • Macrophage lifespan depends on the balance between cell survival and programmed cell death (apoptosis).

Purpose of the Study:

  • To investigate the roles of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in macrophage apoptosis and autophagy.
  • To elucidate the regulatory mechanisms of TRAIL-induced apoptosis and autophagy in macrophages.

Main Methods:

  • Utilized human U937 macrophage cell line.
  • Investigated TRAIL-induced apoptosis and autophagy.
  • Analyzed the roles of death receptors, RIP1 ubiquitination, and caspase-8 variants.
  • Performed RIP1 knockdown experiments.

Main Results:

  • TRAIL induces both apoptosis and autophagy in U937 cells.
  • Autophagy inhibition enhances TRAIL-induced apoptosis, indicating a protective role for autophagy.
  • TRAIL-induced apoptosis and autophagy are mediated by death receptors and regulated by RIP1 ubiquitination and expression.
  • The p43/41-caspase-8 variant is critical for TRAIL-induced autophagy and apoptosis.
  • RIP1 knockdown suppresses macrophage autophagy.

Conclusions:

  • RIP1 is essential for regulating death receptor-mediated autophagy and apoptosis in macrophages.
  • Understanding these pathways offers insights into targeted therapies for cancer, inflammation, and autoimmune diseases.
Keywords:
ApoptosisAutophagyDeathRIP1Tumor necrosis factor-related apoptosis-inducing ligandUbiquitination

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