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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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The kinase activity of PKR represses inflammasome activity

Howard C H Yim1,2, Die Wang1,2, Liang Yu3,2

  • 1Centre for Cancer Research, Hudson Institute of Medical Research, 27-31 Wright St, Clayton, Victoria 3168, Australia.

Cell Research
|January 23, 2016
PubMed

Insights

Protein kinase R (PKR) represses cryopyrin inflammasome activity by inhibiting protein translation, dampening innate immune inflammation. This finding contradicts previous reports and advises against PKR inhibition for treating inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Protein kinase R (PKR) is a key mediator of the antiviral response, regulating protein translation and inflammatory signaling.
  • The precise role of PKR in inflammasome activation, particularly the cryopyrin inflammasome, remains incompletely understood.

Purpose of the Study:

  • To investigate the kinase-dependent and -independent functions of PKR.
  • To determine the role of PKR in regulating cryopyrin inflammasome activity.

Main Methods:

  • Generation of a knock-in mouse model expressing a kinase-inactive mutant of PKR.
  • Utilizing a PKR-deficient mouse model.
  • Assessing cryopyrin inflammasome activity in response to PKR modulation.

Main Results:

  • PKR represses, rather than activates, cryopyrin inflammasome activity, contrary to previous findings.
  • This repression is mediated by PKR's established role in inhibiting protein translation of inflammasome components.
  • PKR prevents inflammasome priming during innate immune signaling.

Conclusions:

  • PKR plays a crucial role in dampening inflammation during innate immune responses.
  • Therapeutic strategies aimed at inhibiting PKR to treat inflammation may be counterproductive.

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