Transcriptome analysis revealed unique genes as targets for the anti-inflammatory action of activated protein C in human macrophages.
BACKGROUND
Activated protein C (APC) has been introduced as a therapeutic agent for treatment of patients with severe sepsis due to its unique anticoagulant and anti-inflammatory properties in the vascular system. In this study we investigated novel targets for the anti-inflammatory action of APC in human macrophages.


METHODS
Using a genome-wide approach, effects of APC on the expression profile in inflammatory activated human macrophages were analyzed.


RESULTS
We identified, for the first time, genes that are specifically regulated by APC under inflammatory conditions, such as chromatin binding protein 4B (CHMP4B) and p300/CBP-associated factor (PCAF), thus indicating a role of APC in the epigenetic control of gene transcription. A functional assay showed the influence of APC in the acetyltransferase/deacetylase activity of nuclear extracts from inflamed macrophages.


CONCLUSIONS
Our data sheds new light on APC targets in inflammation and opens new lines of investigation that may be explored in order to further elucidate its unique molecule properties.
Inflammation Research Unit, Division of Internal Medicine, University Hospital of Zurich and Zurich Center for Integrative Human Physiology ZIHP, University of Zurich, Zurich, Switzerland.
Claudia P
CP
Pereira
Esther B
EB
Bachli
Dominik J
DJ
Schaer
Gabriele
G
Schoedon
D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism*; D011486:Protein C / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D011486:Protein C