Regulation of dectin-1-mediated dendritic cell activation by peroxisome proliferator-activated receptor-gamma ligand troglitazone.

Content Provider	Semantic Scholar
Author	Kock, Grethe Bringmann, Anita Held, Stefanie Andrea Erika Daecke, Solveig Nora Heine, Annkristin Brossart, Peter
Copyright Year	2011
Abstract	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.
Starting Page	101
Ending Page	147
Page Count	47
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.bloodjournal.org/content/bloodjournal/early/2011/02/04/blood-2010-08-302224.full.pdf?sso-checked=true
PubMed reference number	21296999v1
Alternate Webpage(s)	https://doi.org/10.1182/blood-2010-08-302224
DOI	10.1182/blood-2010-08-302224
Journal	Blood
Volume Number	117
Issue Number	13
Language	English
Access Restriction	Open
Subject Keyword	Affinity CLEC7A protein, human Caspase Activation and Recruitment Domain Cytoplasmic matrix Dendritic Cells Down-Regulation Leukemia, B-Cell Ligands Lymphocyte Activation Mitogen-Activated Protein Kinases Mitogens Peroxisome Proliferator-Activated Receptors Peroxisome Proliferators Prostaglandins Prostaglandins, Synthetic Protein Tyrosine Kinase Recombinant Interferon-gamma T-Cell Activation T-Lymphocyte Thiazolidinediones Transcriptional Activation chemokine curdlan cytokine secretion dectin 1 inflammatory response troglitazone
Content Type	Text
Resource Type	Article