PMID- 23531747
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130328
LR  - 20240408
IS  - 1524-5012 (Print)
IS  - 1524-5012 (Linking)
VI  - 13
IP  - 1
DP  - 2013 Spring
TI  - Tumor Necrosis Factor-alpha: Life and Death of Hepatocytes During Liver 
      Ischemia/Reperfusion Injury.
PG  - 119-30
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine 
      involved in a variety of disease pathologies, including ischemia/reperfusion 
      (I/R) injuries in transplantation. The interaction of TNF-alpha with its cognate 
      receptor TNF receptor I (TNFRI) results in the activation of signal transduction 
      pathways that regulate either cell survival or cell death. Hepatocytes express 
      TNFRI and respond to TNF-alpha released by resident Kupffer cells as well as 
      leukocytes that migrate to the liver during I/R injury. Upon binding TNF-alpha, the 
      hepatocyte proliferates or undergoes apoptosis or necroptosis. The decision by 
      the cell to commit to one path or the other is not understood. The damaged tissue 
      exhibits cell death and hemorrhaging from the influx of immune mediators. TNF-alpha 
      inhibitors ameliorate the injury in animal models, suggesting that lowering (but 
      not eliminating) TNF-alpha levels shifts the balance of TNF-alpha toward its beneficial 
      functions. METHODS: We review TNF-alpha signal transduction pathways and the role of 
      TNF-alpha in liver I/R injury. CONCLUSIONS: Because TNF-alpha plays an important role in 
      hepatocyte proliferation, complete inhibition of TNF-alpha is not desirable in 
      treating liver I/R injury. The strategy for developing pharmacological therapies 
      may be the identification of specific intermediates in the TNF-alpha/TNFR1 signal 
      transduction pathway and directed targeting of proapoptotic and pronecroptotic 
      events.
FAU - Shuh, Maureen
AU  - Shuh M
AD  - Laboratory of Transplant Research, Institute of Translational Research, and.
FAU - Bohorquez, Humberto
AU  - Bohorquez H
FAU - Loss, George E Jr
AU  - Loss GE Jr
FAU - Cohen, Ari J
AU  - Cohen AJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ochsner J
JT  - Ochsner journal
JID - 101125795
PMC - PMC3603175
OTO - NOTNLM
OT  - Inflammation
OT  - ischemia
OT  - liver
OT  - reperfusion
OT  - tumor necrosis factor-alpha
COIS- The authors have no financial or proprietary interest in the subject matter of 
      this article.
EDAT- 2013/03/28 06:00
MHDA- 2013/03/28 06:01
PMCR- 2013/03/01
CRDT- 2013/03/28 06:00
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/03/28 06:01 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - TOJ-12-0063 [pii]
PST - ppublish
SO  - Ochsner J. 2013 Spring;13(1):119-30.