PMID- 12842762
OWN - NLM
STAT- MEDLINE
DCOM- 20040312
LR  - 20191107
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 22
IP  - 5
DP  - 2003 Jun 7
TI  - Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-alpha 
      and Fas (CD95).
PG  - 142-8
AB  - Interleukin-18 (IL-18) is a newly identified cytokine with proinflammatory 
      activity. Numerous studies have shown that proinflammatory cytokines may regulate 
      endothelial cells (EC) apoptosis mediated by members of the tumor necrosis factor 
      (TNF) family, such as TNF-alpha and Fas. In this study we hypothesized that IL-18 
      may regulate the susceptibility of liver endothelial cells (LEC) to apoptosis 
      induced by TNF and Fas. IL-18 increased the susceptibility of LEC to undergo 
      apoptosis mediated by TNF but not by Fas. Since TNF-induced apoptosis is mediated 
      by the type I TNF receptor (TNFRI), we investigated up-regulation of this 
      receptor in IL-18-treated LEC. IL-18 induced up-regulation of the TNFRI on the 
      surface of LEC. Partial blocking of LEC apoptosis induced by IL-18 and TNF was 
      observed when the cells were pretreated with the broad-spectrum inhibitor of 
      caspases z-VAD-fmk, suggesting involvement of the caspase pathway in apoptosis 
      induced by these cytokines in these cells. Our results show that IL-18 
      differentially regulates apoptosis mediated by the death-inducing factors, TNF 
      and Fas. To our knowledge, this is the first report that IL-18 may regulate 
      endothelial cell apoptosis mediated by TNF. These results may have clinical 
      implications in those clinical hepatic conditions associated with high levels of 
      IL-18 and TNF.
FAU - Marino, Eliana
AU  - Marino E
AD  - Laboratorio de Patologia Celular y Molecular, Centro de Medicina Experimental, 
      Instituto Venezolano de Investigaciones Cientificas (IVIC), Apartado 21827, 
      Caracas 1020-A, Venezuela.
FAU - Cardier, Jose E
AU  - Cardier JE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Antigens, CD)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Interleukin-18)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/metabolism
MH  - Apoptosis/*drug effects
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cricetinae
MH  - Endothelial Cells/cytology/*drug effects
MH  - Flow Cytometry
MH  - Fluorescence
MH  - Gene Expression
MH  - Interleukin-18/*pharmacology
MH  - Mice
MH  - Receptors, Tumor Necrosis Factor/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Recombinant Proteins/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
MH  - fas Receptor/genetics/*metabolism
EDAT- 2003/07/05 05:00
MHDA- 2004/03/16 05:00
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2004/03/16 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
AID - S1043466603001509 [pii]
AID - 10.1016/s1043-4666(03)00150-9 [doi]
PST - ppublish
SO  - Cytokine. 2003 Jun 7;22(5):142-8. doi: 10.1016/s1043-4666(03)00150-9.