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Title: Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D
Authors: Ferreira, Gabriela B
van Etten, Evelyne
Lage, Kasper
Hansen, Daniel Aaen
Moreau, Yves
Workman, Christopher T
Waer, Mark
Verstuyf, Annemieke
Waelkens, Etienne
Overbergh, Lutgart ×
Mathieu, Chantal #
Issue Date: Jul-2009
Publisher: WILEY-VCH Verlag
Series Title: Proteomics vol:9 issue:14 pages:3752-3764
Abstract: Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence or absence of TX527 (10(-8) M) (n=4). Protein samples were separated into two different pH ranges (pH4-7 and 6-9), analyzed by 2-D DIGE and differentially expressed spots (p<0.01) were identified by MALDI-TOF/TOF (76.3 and 70.7% in iDC and mature DCs, respectively). Differential protein expression revealed three protein groups predominantly affected by TX527 treatment, namely proteins involved in cytoskeleton structure, in protein biosynthesis/proteolysis and in metabolism. Moreover, protein interactome-network analysis demonstrated close interaction between these different groups (p<0.001) and morphological and functional analyses confirmed the integrated effect of TX527 on human DCs, resulting in a cell with altered morphology, cell surface marker expression, endocytic and migratory capacity.
URI: 
ISSN: 1615-9853
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Laboratory of Experimental Transplantation
Laboratory of Protein Phosphorylation and Proteomics
Medical Clerkships Centers
Laboratory of Phosphoproteomics (-)
× corresponding author
# (joint) last author

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