Regulation of dectin-1–mediated dendritic cell activation by peroxisome proliferator–activated receptor-gamma ligand troglitazone
| Autor: | Grethe Kock, Solveig Nora Daecke, Peter Brossart, Anita Bringmann, Annkristin Heine, Stefanie Andrea Erika Held |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Chemokine
MAP Kinase Signaling System Immunology Drug Evaluation Preclinical Peroxisome proliferator-activated receptor Syk Nerve Tissue Proteins Biology Ligands Biochemistry Troglitazone chemistry.chemical_compound medicine Humans Hypoglycemic Agents Syk Kinase Lectins C-Type Lymphocytes Chromans Protein kinase A Cells Cultured Cyclopentenone prostaglandins Cell Proliferation chemistry.chemical_classification Membrane Glycoproteins Intracellular Signaling Peptides and Proteins Membrane Proteins Dendritic Cells Cell Biology Hematology Protein-Tyrosine Kinases Cell biology CARD Signaling Adaptor Proteins PPAR gamma chemistry biology.protein Cytokines Thiazolidinediones Cytokine secretion Chemokines Signal transduction medicine.drug |
| Zdroj: | Blood. 117:3569-3574 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2010-08-302224 |
| Popis: | Dectin-1 is the major receptor for fungal β-glucans. The activation of Dectin-1 leads to the up-regulation of surface molecules on dendritic cells (DCs) and cytokine secretion. Furthermore, Dectin-1 is important for the recruitment of leukocytes and the production of inflammatory mediators. Peroxisome proliferator–activated receptor-γ (PPAR-γ) and its ligands, cyclopentenone prostaglandins or thiazolidinediones, have modulatory effects on B-cell, T-cell, and DC function. In the present study, we analyzed the effects of troglitazone (TGZ), a high-affinity synthetic PPAR-γ ligand, on the Dectin-1–mediated activation of monocyte-derived human DCs. Dectin-1–mediated activation of DCs was inhibited by TGZ, as shown by down-regulation of costimulatory molecules and reduced secretion of cytokines and chemokines involved in T-lymphocyte activation. Furthermore, TGZ inhibited the T-cell–stimulatory capacity of DCs. These effects were not due to a diminished expression of Dectin-1 or to a reduced phosphorylation of spleen tyrosine kinase; they were mediated by the inhibition of downstream signaling molecules such as mitogen-activated protein kinases and nuclear factor-κB. Furthermore, curdlan-mediated accumulation of caspase recruitment domain 9 (CARD9) in the cytosol was inhibited by TGZ. Our data demonstrate that the PPAR-γ ligand TGZ inhibits Dectin-1–mediated activation by interfering with CARD9, mitogen-activated protein kinase, and nuclear factor-κB signaling pathways. This confirms their important role as negative-feedback regulators of potentially harmful inflammatory responses. |
| Databáze: | OpenAIRE |
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