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A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.

Publication ,  Journal Article
Daniel, S; Arvelo, MB; Patel, VI; Longo, CR; Shrikhande, G; Shukri, T; Mahiou, J; Sun, DW; Mottley, C; Grey, ST; Ferran, C
Published in: Blood
October 15, 2004

A20 is a stress response gene in endothelial cells (ECs). A20 serves a dual cytoprotective function, protecting from tumor necrosis factor (TNF)-mediated apoptosis and inhibiting inflammation via blockade of the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we evaluated the molecular basis of the cytoprotective function of A20 in EC cultures and questioned whether its protective effect extends beyond TNF to other apoptotic and necrotic stimuli. Our data demonstrate that A20 targets the TNF apoptotic pathway by inhibiting proteolytic cleavage of apical caspases 8 and 2, executioner caspases 3 and 6, Bid cleavage, and release of cytochrome c, thus preserving mitochondrion integrity. A20 also protects from Fas/CD95 and significantly blunts natural killer cell-mediated EC apoptosis by inhibiting caspase 8 activation. In addition to protecting ECs from apoptotic stimuli, A20 safeguards ECs from complement-mediated necrosis. These data demonstrate, for the first time, that the cytoprotective effect of A20 in ECs is not limited to TNF-triggered apoptosis. Rather, A20 affords broad EC protective functions by effectively shutting down cell death pathways initiated by inflammatory and immune offenders.

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

October 15, 2004

Volume

104

Issue

8

Start / End Page

2376 / 2384

Location

United States

Related Subject Headings

  • fas Receptor
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Swine
  • Signal Transduction
  • Proteins
  • Nuclear Proteins
  • Necrosis
  • NF-kappa B
  • Mitochondria
 

Citation

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Daniel, S., Arvelo, M. B., Patel, V. I., Longo, C. R., Shrikhande, G., Shukri, T., … Ferran, C. (2004). A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation. Blood, 104(8), 2376–2384. https://doi.org/10.1182/blood-2003-02-0635
Daniel, Soizic, Maria B. Arvelo, Virendra I. Patel, Christopher R. Longo, Gautam Shrikhande, Tala Shukri, Jerome Mahiou, et al. “A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.Blood 104, no. 8 (October 15, 2004): 2376–84. https://doi.org/10.1182/blood-2003-02-0635.
Daniel S, Arvelo MB, Patel VI, Longo CR, Shrikhande G, Shukri T, et al. A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation. Blood. 2004 Oct 15;104(8):2376–84.
Daniel, Soizic, et al. “A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.Blood, vol. 104, no. 8, Oct. 2004, pp. 2376–84. Pubmed, doi:10.1182/blood-2003-02-0635.
Daniel S, Arvelo MB, Patel VI, Longo CR, Shrikhande G, Shukri T, Mahiou J, Sun DW, Mottley C, Grey ST, Ferran C. A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation. Blood. 2004 Oct 15;104(8):2376–2384.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

October 15, 2004

Volume

104

Issue

8

Start / End Page

2376 / 2384

Location

United States

Related Subject Headings

  • fas Receptor
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Swine
  • Signal Transduction
  • Proteins
  • Nuclear Proteins
  • Necrosis
  • NF-kappa B
  • Mitochondria