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PPAR-γ agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-κB pathways
被引:151
作者:

Appel, S
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Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany

Mirakaj, V
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Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany

Bringmann, A
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机构:
Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany

Weck, MM
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机构:
Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany

Grünebach, F
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h-index: 0
机构:
Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany

Brossart, P
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Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany
机构:
[1] Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany
来源:
关键词:
D O I:
10.1182/blood-2004-12-4709
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Dendritic cells (DCs) play an important role in initiating and maintaining primary immune responses. However, mechanisms involved in the resolution of these responses are elusive. We analyzed the effects of 15d-PGJ(2) and the synthetic peroxisome proliferator-activated receptor (PPAR)-gamma ligand troglitazone (TGZ) on the immunogenicity of human monocytederived DCs upon stimulation with toll-like receptor (TLR) ligands. Activation of PPAR-gamma resulted in a reduced stimulation of DCs via the TLR ligands 2, 3, 4, and 7, characterized by down-regulation of costimulatory and adhesion molecules and reduced secretion of cytokines and chemokines involved in T-lymphocyte activation and recruitment. MCP-1 (monocyte chernotactic protein-1) production was increased due to PPAR-gamma activation. Furthermore, TGZ-treated DCs showed a significantly reduced capacity to stimulate T-cell proliferation, emphasizing the inhibitory effect of PPAR-gamma activation on TLR-induced DC maturation. Western blot analyses revealed that these inhibitory effects on TLR-induced DC activation were mediated via inhibition of the NF-kappa B and mitogen-activated protein (MAP) kinase pathways while not affecting the PI3 kinase/Akt signaling. Our data demonstrate that inhibition of the MAP kinase and NF-kappa B pathways is critically involved in the regulation of TLR and PPAR-gamma-mediated signaling in DCs.
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页码:3888 / 3894
页数:7
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