PMID- 12629330
OWN - NLM
STAT- MEDLINE
DCOM- 20030701
LR  - 20191025
IS  - 0954-6928 (Print)
IS  - 0954-6928 (Linking)
VI  - 14
IP  - 1
DP  - 2003 Feb
TI  - Dual response to Fas ligation in human endothelial cells: apoptosis and induction 
      of chemokines, interleukin-8 and monocyte chemoattractant protein-1.
PG  - 89-94
AB  - BACKGROUND: To maintain the integrity of tissues, endothelial cells play critical 
      roles. Fas ligand (FasL) is well known to deliver a death signal through its 
      receptor, Fas. The Fas/FasL system may concomitantly induce expressions of 
      interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) besides 
      triggering apoptosis in endothelial cells. We also investigated whether an 
      inhibitor of caspase-8 (Z-IETD-FMK) does modulate IL-8 and MCP-1 secretion. 
      METHODS AND RESULTS: After treatment with interferon-gamma (IFN-gamma), human 
      recombinant FasL (hr FasL) or Fas agonistic antibody (CH-11) was added to 
      cultured human endothelial cells. IFN-gamma up-regulated Fas mRNA levels. Fas 
      ligation promoted apoptosis assessed by fluorescent-activated cell sorter (FACS) 
      analysis in a dose-dependent manner and induced prominent DNA fragmentation. 
      Simultaneously, IL-8 and MCP-1 were secreted from the endothelial cells in 
      response to hr FasL or CH-11 in a dose-dependent manner (P < 0.01). 
      Fas-neutralizing agent (Fas-Fc) suppressed the Fas-mediated secretions of IL-8 
      and MCP-1 (P < 0.01) both as well as the Fas-mediated apoptosis. On the other 
      hand, whereas Z-IETD-FMK suppressed apoptosis, the inhibitor enhanced the 
      Fas-mediated secretions of both IL-8 and MCP-1 beyond the value of the Fas 
      stimulation alone (P < 0.01), suggesting an enhanced signalling for the chemokine 
      expression. CONCLUSION: In human endothelial cells, the Fas/FasL system induces 
      both IL-8 and MCP-1 secretions probably via a caspase-8 independent pathway. The 
      Fas/FasL system may amplify the inflammatory cascade in the vascular injury and 
      atherogenesis by recruiting leukocytes at the region of apoptotic endothelial 
      damage.
FAU - Yamaoka-Tojo, Minako
AU  - Yamaoka-Tojo M
AD  - The First Department of Internal Medicine, Yamagata University School of 
      Medicine, Japan. myamaokoa@med.kitasato-u.ac.jp
FAU - Yamaguchi, Seiji
AU  - Yamaguchi S
FAU - Nitobe, Joji
AU  - Nitobe J
FAU - Abe, Shuichi
AU  - Abe S
FAU - Inoue, Sumito
AU  - Inoue S
FAU - Nozaki, Naoki
AU  - Nozaki N
FAU - Okuyama, Masaki
AU  - Okuyama M
FAU - Sata, Makoto
AU  - Sata M
FAU - Kubota, Isao
AU  - Kubota I
FAU - Nakamura, Hidenori
AU  - Nakamura H
FAU - Tomoike, Hitonobu
AU  - Tomoike H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Coron Artery Dis
JT  - Coronary artery disease
JID - 9011445
RN  - 0 (Chemokine CCL2)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Interleukin-8)
RN  - 0 (Membrane Glycoproteins)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - DNA Fragmentation
MH  - Endothelium, Vascular/*cytology/*physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fas Ligand Protein
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - Membrane Glycoproteins/*physiology
EDAT- 2003/03/12 04:00
MHDA- 2003/07/02 05:00
CRDT- 2003/03/12 04:00
PHST- 2003/03/12 04:00 [pubmed]
PHST- 2003/07/02 05:00 [medline]
PHST- 2003/03/12 04:00 [entrez]
AID - 10.1097/00019501-200302000-00010 [doi]
PST - ppublish
SO  - Coron Artery Dis. 2003 Feb;14(1):89-94. doi: 10.1097/00019501-200302000-00010.