PMID- 14666382
OWN - NLM
STAT- MEDLINE
DCOM- 20040628
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 53
IP  - 6
DP  - 2004 Jun
TI  - Vascular endothelial growth factor inhibits maturation of dendritic cells induced 
      by lipopolysaccharide, but not by proinflammatory cytokines.
PG  - 543-50
AB  - PURPOSE: Dendritic cells (DCs) play an important role in the host's 
      immunosurveillance against cancer. It has been shown that the function of DCs is 
      impaired and their population decreased in a cancer-bearing host. In the present 
      study, we investigated the mechanism of down-regulation of DCs in a 
      cancer-bearing host. METHODS: We evaluated the relationship between DC 
      infiltration and production of vascular endothelial growth factor (VEGF) in 
      carcinoma tissue by immunohistochemistry. Furthermore, functional and 
      phenotypical alterations of DCs were evaluated when monocyte-derived, mature DCs 
      were treated with VEGF in vitro. Monocyte-derived DCs were generated in a culture 
      of monocyte with interleukin 4 (IL-4) and granulocyte-macrophage 
      colony-stimulating factor, and the maturation of DCs was induced by either 
      lipopolysaccharide (LPS) or a proinflammatory cytokine cocktail: tumor-necrosis 
      factor alpha, prostaglandin E2, IL-6, and IL-1beta. RESULTS: A significant 
      inverse correlation was found between the density of DCs and the quantity of VEGF 
      production in gastric carcinoma tissue (r=-0.39, p<0.05). In LPS-induced 
      maturation, the ability of mature DCs to stimulate allogenic T cells and produce 
      IL-12 (p70 heterodimer) was suppressed by the addition of VEGF in a 
      dose-dependent manner. A lesser expression of costimulatory molecules (CD80 and 
      CD86) was seen in DCs treated with exogenous VEGF than in DCs not treated with 
      VEGF. The population of dead DCs (early and late apoptosis) treated with VEGF 
      increased more than that without VEGF treatment, using the annexin V and 
      propidium iodide evaluation in DCs matured by LPS. In contrast, in DCs matured by 
      the proinflammatory cytokine cocktail, the down-regulation of costimulatory 
      molecules and induction of DC apoptosis was not seen. CONCLUSIONS: These findings 
      show that the inhibition of DC maturation by VEGF differs depending on the 
      maturation status of the DCs.
FAU - Takahashi, Akihiro
AU  - Takahashi A
AD  - First Department of Surgery, University of Yamanashi, 1110 Shimokato, 409-3898 
      Tamaho, Yamanashi, Japan.
FAU - Kono, Koji
AU  - Kono K
FAU - Ichihara, Fumiko
AU  - Ichihara F
FAU - Sugai, Hidemitsu
AU  - Sugai H
FAU - Fujii, Hideki
AU  - Fujii H
FAU - Matsumoto, Yoshiro
AU  - Matsumoto Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031210
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Oxytocics)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adenocarcinoma/*immunology/pathology/surgery
MH  - Angiogenesis Inhibitors/metabolism
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Dendritic Cells/*drug effects/immunology
MH  - Dinoprostone/pharmacology
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-12/metabolism
MH  - Interleukin-6/pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Oxytocics/pharmacology
MH  - Phenotype
MH  - Stomach Neoplasms/*immunology/pathology/surgery
MH  - T-Lymphocytes/drug effects/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Vascular Endothelial Growth Factor A/metabolism/*pharmacology
MH  - Vascular Endothelial Growth Factor Receptor-2/metabolism
PMC - PMC11034272
EDAT- 2003/12/11 05:00
MHDA- 2004/06/29 05:00
PMCR- 2003/12/10
CRDT- 2003/12/11 05:00
PHST- 2003/08/21 00:00 [received]
PHST- 2003/10/17 00:00 [accepted]
PHST- 2003/12/11 05:00 [pubmed]
PHST- 2004/06/29 05:00 [medline]
PHST- 2003/12/11 05:00 [entrez]
PHST- 2003/12/10 00:00 [pmc-release]
AID - 466 [pii]
AID - 10.1007/s00262-003-0466-8 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2004 Jun;53(6):543-50. doi: 10.1007/s00262-003-0466-8. 
      Epub 2003 Dec 10.