A novel TNFR1-triggered apoptosis pathway mediated by class IA PI3Ks in neutrophils

Geering, Barbara; Gurzeler, Ursina; Federzoni, Elena; Kaufmann, Thomas; Simon, Hans-Uwe (2011). A novel TNFR1-triggered apoptosis pathway mediated by class IA PI3Ks in neutrophils. Blood, 117(22), pp. 5953-5962. Washington, D.C.: American Society of Hematology 10.1182/blood-2010-11-322206

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The most common form of neutrophil death is apoptosis. In the present study, we report surprising differences in the molecular mechanisms used for caspase activation between FAS/CD95-stimulated and TNF receptor 1 (TNFR1)-stimulated neutrophils. Whereas FAS-induced apoptosis was followed by caspase-8 activation and required Bid to initiate the mitochondrial amplification loop, TNF-?-induced apoptosis involved class IA PI3Ks, which were activated by MAPK p38. TNF-?-induced PI3K activation resulted in the generation of reactive oxygen species, which activated caspase-3, a mechanism that did not operate in neutrophils without active NADPH oxidase. We conclude that in neutrophils, proapoptotic pathways after TNFR1 stimulation are initiated by p38 and PI3K, but not by caspase-8, a finding that should be considered in anti-inflammatory drug-development strategies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Gurzeler, Ursina; Kaufmann, Thomas and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:18

Last Modified:

02 Dec 2015 13:21

Publisher DOI:

10.1182/blood-2010-11-322206

PubMed ID:

21478427

Web of Science ID:

000291203200023

BORIS DOI:

10.7892/boris.5462

URI:

https://boris.unibe.ch/id/eprint/5462 (FactScience: 210209)

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