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Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
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Necrosis-dependent and independent signaling of the RIP kinases in inflammation

Kenta Moriwaki1, Francis K M Chan1

  • 1Department of Pathology, University of Massachusetts Medical School, Immunology and Microbiology Program, Worcester, MA 01605, USA.

Cytokine & Growth Factor Reviews
|January 14, 2014
PubMed

Insights

Receptor-interacting protein kinases (RIPK1 and RIPK3) regulate cell death and inflammation. Emerging evidence suggests RIPK1 and RIPK3 also control apoptosis and cytokine production independently of necrosis, requiring re-interpretation of disease models.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Regulated necrosis, a programmed cell death pathway, is mediated by receptor-interacting protein kinase 1 (RIPK1) and RIPK3.
  • RIPK1 and RIPK3 have been implicated in infectious and sterile inflammatory diseases, often attributed to their role in necrosis.

Purpose of the Study:

  • To re-evaluate the established roles of RIPK1 and RIPK3 in inflammatory diseases.
  • To highlight the need to consider both cell death-dependent and independent functions of RIP kinases.

Main Methods:

  • Review of existing literature on RIPK1 and RIPK3 signaling.
  • Analysis of data from studies using RIPK1 inhibitors (e.g., Necrostatin-1) and RIPK3-deficient models.

Main Results:

  • Emerging evidence indicates RIPK1 kinase activity and RIPK3 can regulate apoptosis and inflammatory cytokine production independently of necrosis.
  • Phenotypes observed in RIPK1 or RIPK3 loss-of-function models may not solely depend on necrosis.

Conclusions:

  • Conclusions drawn from RIPK1 and RIPK3 deficiency studies in vivo may require re-interpretation.
  • Future research on RIPK1 and RIPK3 in inflammatory responses must account for both cell death-dependent and independent mechanisms.
Keywords:
Caspase 8FaddInflammasomeMLKLNF-κBTNF

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