PMID- 11313377
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 166
IP  - 9
DP  - 2001 May 1
TI  - The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced 
      cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells.
PG  - 5407-15
AB  - TNF-alpha-related apoptosis-inducing ligand (TRAIL) is characterized by its 
      preferential induction of apoptosis of tumor cells but not normal cells. 
      Dendritic cells (DCs), besides their role as APCs, now have been demonstrated to 
      exert cytotoxicity or cytostasis on some tumor cells. Here, we report that both 
      human CD34(+) stem cell-derived DCs (CD34DCs) and human CD14(+) monocyte-derived 
      DCs (MoDCs) express TRAIL and exhibit cytotoxicity to some types of tumor cells 
      partially through TRAIL. Moderate expression of TRAIL appeared on CD34DCs from 
      the 8th day of culture and was also seen on freshly isolated monocytes. The level 
      of TRAIL expression remained constant until DC maturation. TRAIL expression on 
      immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation. 
      Moreover, IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to 
      kill TRAIL-sensitive tumor cells, but LPS did not have such an effect. The 
      up-regulation of TRAIL on IFN-beta-stimulated DCs partially contributed to the 
      increased cytotoxicity of DCS: Pretreatment of TRAIL-sensitive tumor cells with 
      caspase-3 inhibitor could significantly increase their resistance to the 
      cytotoxicity of IFN-beta-stimulated DCS: In contrast, NF-kappaB inhibitor could 
      significantly increase the sensitivity of tumor cells to the killing by 
      nonstimulated or LPS-stimulated DCS: Our studies demonstrate that 
      IFN-beta-stimulated DCs are functionally cytotoxic. Thus, an innate mechanism of 
      DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors 
      to directly kill tumor cells partially via TRAIL. Subsequently, DCs act as APCs 
      involved in the uptake, processing, and presentation of apoptotic tumor Ags to 
      cross-prime CD8(+) CTL cells.
FAU - Liu, S
AU  - Liu S
AD  - Department of Immunology, Second Military Medical University, Shanghei, People's 
      Republic of China.
FAU - Yu, Y
AU  - Yu Y
FAU - Zhang, M
AU  - Zhang M
FAU - Wang, W
AU  - Wang W
FAU - Cao, X
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens, CD34)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Adjuvants, Immunologic/pharmacology/physiology
MH  - Antigens, CD34/biosynthesis
MH  - Apoptosis/*immunology
MH  - Apoptosis Regulatory Proteins
MH  - Caspase 3
MH  - Caspases/metabolism/physiology
MH  - Cells, Cultured
MH  - *Cytotoxicity, Immunologic
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Enzyme Activation/immunology
MH  - Growth Inhibitors/physiology
MH  - HL-60 Cells
MH  - Hematopoietic Stem Cells/immunology/pathology
MH  - Humans
MH  - Interferon-beta/*pharmacology
MH  - Jurkat Cells
MH  - Ligands
MH  - Membrane Glycoproteins/biosynthesis/*physiology
MH  - Monocytes/cytology/immunology/metabolism
MH  - NF-kappa B/metabolism/physiology
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Cells, Cultured/enzymology/*immunology/*pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*physiology
MH  - U937 Cells
MH  - Up-Regulation/immunology
EDAT- 2001/04/21 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/04/21 10:00
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - 10.4049/jimmunol.166.9.5407 [doi]
PST - ppublish
SO  - J Immunol. 2001 May 1;166(9):5407-15. doi: 10.4049/jimmunol.166.9.5407.