PMID- 17210619
OWN - NLM
STAT- MEDLINE
DCOM- 20070604
LR  - 20220330
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 81
IP  - 4
DP  - 2007 Apr
TI  - Splanchnic ischemia and reperfusion injury is reduced by genetic or 
      pharmacological inhibition of TNF-alpha.
PG  - 1032-43
AB  - In the present study, we used TNF-alpha receptor 1 knockout (TNF-alphaR1KO) mice 
      to evaluate a possible role of TNF-alpha on the pathogenesis of ischemia and 
      reperfusion injury of the multivisceral organs. Ischemia and reperfusion injury 
      was induced in mice by clamping the superior mesenteric artery and the celiac 
      artery for 30 min, followed thereafter by reperfusion. Sixty minutes after 
      reperfusion, animals were killed for histological examination and biochemical 
      studies. Injured wild-type (WT) mice developed a significant increase of ileum 
      TNF-alpha levels, myeloperoxidase activity, and marked histological injury and 
      apoptosis. Ischemia and reperfusion injury of the multivisceral organs was also 
      associated with a significant mortality. Reperfused ileum sections from injured 
      WT mice showed positive staining for P-selectin, VCAM, ICAM-1, and E-selectin. 
      The intensity and degree of P-selectin, E-selectin, VCAM, and ICAM-1 were reduced 
      markedly in tissue sections from injured TNF-alphaR1KO mice. Ischemia and 
      reperfusion-injured TNF-alphaR1KO mice also showed a significant reduction of 
      neutrophil infiltration into the intestine, a reduction of apoptosis, an improved 
      histological status of the intestine, and survival. In addition, we investigated 
      the effect of Etanercept, a TNF-alpha soluble receptor construct, on ischemia and 
      reperfusion injury of the multivisceral organs. Etanercept (5 mg/kg administered 
      i.p. 5 min prior to reperfusion) significantly reduced the inflammatory response 
      and the ileum injury. Taken together, our results clearly demonstrate that 
      TNF-alpha plays an important role in the ischemia and reperfusion injury and put 
      forward the hypothesis that modulation of TNF-alpha expression may represent a 
      novel and possible strategy.
FAU - Esposito, Emanuela
AU  - Esposito E
AD  - Department of Experimental Pharmacy, University of Naples Federico II, Italy.
FAU - Mazzon, Emanuela
AU  - Mazzon E
FAU - Muia, Carmelo
AU  - Muia C
FAU - Meli, Rosaria
AU  - Meli R
FAU - Sessa, Edoardo
AU  - Sessa E
FAU - Cuzzocrea, Salvatore
AU  - Cuzzocrea S
LA  - eng
PT  - Journal Article
DEP - 20070108
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Adhesion Molecules/metabolism
MH  - Etanercept
MH  - Fas Ligand Protein/metabolism
MH  - Immunoglobulin G/*pharmacology
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/*pharmacology
MH  - Intestines/cytology/physiology
MH  - Ischemia/*genetics/mortality/therapy
MH  - Lipid Peroxidation
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophil Infiltration
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Reperfusion Injury/*genetics/mortality/therapy
MH  - *Splanchnic Circulation
MH  - Tumor Necrosis Factor-alpha/antagonists & 
      inhibitors/genetics/metabolism/*physiology
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2007/01/11 09:00
MHDA- 2007/06/05 09:00
CRDT- 2007/01/11 09:00
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/06/05 09:00 [medline]
PHST- 2007/01/11 09:00 [entrez]
AID - jlb.0706480 [pii]
AID - 10.1189/jlb.0706480 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2007 Apr;81(4):1032-43. doi: 10.1189/jlb.0706480. Epub 2007 Jan 8.