Abstract:
:TNF is a master proinflammatory cytokine whose pathogenic role in inflammatory disorders has long been attributed to induction of proinflammatory mediators. TNF also activates cell survival and death pathways, and recent studies demonstrated that TNF also causes inflammation by inducing cell death. The default response of most cells to TNF is survival and NF-κB-mediated upregulation of prosurvival molecules is a well-documented protective mechanism downstream of TNFR1. Recent studies revealed the existence of an NF-κB-independent cell death checkpoint that restricts cell demise by inactivating RIPK1. Disruption of this checkpoint leads to RIPK1 kinase-dependent death and causes inflammation in vivo. These revelations bring complexity to the control of TNF-induced cell death, and suggest clinical benefit of RIPK1 inhibitors in TNF-driven human inflammatory disorders.
journal_name
Trends Immunoljournal_title
Trends in immunologyauthors
Ting AT,Bertrand MJMdoi
10.1016/j.it.2016.06.002subject
Has Abstractpub_date
2016-08-01 00:00:00pages
535-545issue
8eissn
1471-4906issn
1471-4981pii
S1471-4906(16)30057-6journal_volume
37pub_type
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