Abstract
OBJECTIVE: The protein C anticoagulant pathway is an essential process for attenuating thrombin generation by the membrane-bound procoagulant complexes tenase and prothrombinase. In this pathway, protein S (PS) serves as a cofactor for activated protein C. PS circulates in plasma both in a free form and in complex with complement component 4b-binding protein (C4BP). C4BP is a known acute phase reactant, thereby suggesting a relation between PS and the acute phase response. Interleukin (IL)-6 has been shown to increase both PS and C4BP gene expression. Our objective was to study the regulation of PS gene expression by IL-6 in detail.
METHODS AND RESULTS: IL-6 upregulates both PS mRNA and protein levels in liver-derived HepG2 cells. The promoter of the PS gene (PROS1) was cloned upstream from a luciferase reporter gene. After transfection in HepG2 cells, the luciferase activity was shown to be stimulated by the addition of IL-6. IL-6 exerts its effect through Signal Transducer and Activator of Transcription 3 (STAT3) that interacts with the PROS1 promoter at a binding site in between nucleotides 229 to 207 upstream from the translational start.
CONCLUSIONS: IL-6 induces PS expression via STAT3. A possible function for IL-6-induced PS expression in cell survival is discussed.
Original language | English |
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Pages (from-to) | 2168-74 |
Number of pages | 7 |
Journal | Arteriosclerosis, Thrombosis and Vascular Biology |
Volume | 26 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2006 |
Externally published | Yes |
Keywords
- Cell Line, Tumor
- Gene Expression Regulation
- Humans
- Interleukin-6
- Phosphorylation
- Promoter Regions, Genetic
- Protein S
- RNA, Messenger
- Response Elements
- STAT3 Transcription Factor