Transcriptome Analysis Revealed Unique Genes as Targets for the Anti-inflammatory Action of Activated Protein C in Human Macrophages

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