PMID- 12393527
OWN - NLM
STAT- MEDLINE
DCOM- 20030313
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 4
DP  - 2003 Feb 15
TI  - Stem cell factor increases the expression of FLIP that inhibits IFNgamma -induced 
      apoptosis in human erythroid progenitor cells.
PG  - 1324-8
AB  - Interferon gamma (IFNgamma) acts on human erythroid colony-forming cells (ECFCs) 
      to up-regulate Fas, without a demonstrable change of Fas ligand (FasL) or 
      Fas-associated DD-containing protein (FADD) expression and activates caspase-8 
      plus caspase-3, which produce apoptosis. Our previous data showed that stem cell 
      factor (SCF) reduced the inhibitory effect of IFNgamma on human ECFCs when both 
      factors were present in the cultures. However, the mechanism by which SCF 
      prevents IFNgamma-induced apoptosis in ECFCs is unclear. In this study we used 
      highly purified human ECFCs to investigate the mechanism of the effect of SCF on 
      IFNgamma-induced apoptosis. Because the binding of FasL to Fas is the first step 
      of the apoptosis cascade and IFNgamma strongly up-regulates Fas expression, we 
      added FasL (50 ng/mL) to the cultures with IFNgamma to accentuate the 
      IFNgamma-induced activation of caspase-8 and caspase-3 plus subsequent apoptosis. 
      SCF (100 ng/mL) clearly inhibited the activation of caspase-8 and caspase-3 
      induced by IFNgamma and/or FasL, and it also reduced apoptosis as measured by the 
      terminal dUTP nick-end labeling (TUNEL) assay. SCF did not decrease the surface 
      expression of Fas on the ECFCs. FADD-like interleukin 1 beta 
      (IL-1beta)-converting enzyme (FLICE)-inhibitory protein (FLIP) has been reported 
      to interact with FADD and/or caspase-8 at the death-inducing signaling complex 
      (DISC) level following Fas stimulation and acts as a dominant-negative caspase-8. 
      SCF increased FLIP mRNA and protein expression, concomitant with reduced 
      apoptosis, whereas IFNgamma and/or FasL did not change FLIP expression. Reduction 
      of FLIP expression with antisense oligonucleotides decreased the capacity of SCF 
      to inhibit IFNgamma-induced apoptosis, demonstrating a definite role for FLIP in 
      the SCF-induced protection of ECFCs from IFNgamma-initiated apoptosis.
FAU - Chung, Ik-Joo
AU  - Chung IJ
AD  - Department of Veterans Affairs Medical Service, Division of Hematology/Oncology, 
      Nashville, TN, USA.
FAU - Dai, Chunhua
AU  - Dai C
FAU - Krantz, Sanford B
AU  - Krantz SB
LA  - eng
GR  - 2 T32-DK-07186/DK/NIDDK NIH HHS/United States
GR  - CA-68485/CA/NCI NIH HHS/United States
GR  - R01 DK-15555/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021010
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (CFLAR protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (Stem Cell Factor)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein
MH  - Carrier Proteins/analysis/*genetics
MH  - Caspase 3
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Enzyme Activation/drug effects
MH  - Erythroid Precursor Cells/*cytology
MH  - Fas Ligand Protein
MH  - Gene Expression/drug effects
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Interferon-gamma/*pharmacology
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Membrane Glycoproteins/pharmacology
MH  - Oligonucleotides, Antisense/pharmacology
MH  - RNA, Messenger/analysis
MH  - Stem Cell Factor/*pharmacology
EDAT- 2002/10/24 04:00
MHDA- 2003/03/14 04:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/03/14 04:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0006-4971(20)57393-X [pii]
AID - 10.1182/blood-2002-06-1720 [doi]
PST - ppublish
SO  - Blood. 2003 Feb 15;101(4):1324-8. doi: 10.1182/blood-2002-06-1720. Epub 2002 Oct 
      10.