Comprehensive Assessment of
Proteins Regulated by
Dexamethasone Reveals Novel Effects in Primary Human Peripheral Blood
Mononuclear Cells
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Abstract
Inflammation
is a physiological process involved in many diseases.
Monitoring proteins involved in regulatory effects may help to improve
our understanding of inflammation. We have analyzed proteome alterations
induced in peripheral blood mononuclear cells (PBMCs) upon inflammatory
activation in great detail using high-resolution mass spectrometry.
Moreover, the activated cells were treated with dexamethasone to investigate
their response to this antiphlogistic drug. From a total of 6886 identified
proteins, 469 proteins were significantly regulated upon inflammatory
activation. Data are available via ProteomeXchange with identifiers
PXD001415–23. Most of these proteins were counter-regulated
by dexamethasone, with some exceptions concerning members of the interferon-induced
protein family. To confirm some of these results, we performed targeted
MRM analyses of selected peptides. The inflammation-induced upregulation
of proteins such as IL-1β, IL-6, CXCL2, and GROα was confirmed,
however, with strong quantitative interindividual differences. Furthermore,
the inability of dexamethasone to downregulate inflammation-induced
proteins such as PTX3 and TSG6 was clearly demonstrated. In conclusion,
the relation of cell function as well as drug-induced modulation thereof
was successfully mapped to proteomes, suggesting targeted analysis
as a novel and powerful drug evaluation method. Although most consequences
of dexamethasone were found to be compatible with the expected mode
of action, some unexpected but significant observations may be related
to adverse effects