Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk.
High level of fibrinogen in plasma is recognised as an important vascular risk factor. However, it is not known if the increase in fibrinogen is directly responsible for the vascular risk or is a marker of vascular inflammation. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on vascular injury was noted. Among the cytokines which induce the synthesis of fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human hepatoma cell line). Interestingly at the same concentrations needed for fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect against vascular injury leading to atherosclerosis, dose dependently down regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6 induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in fibrinogen secretion in the medium and beta chain mRNA expression and to an inhibition of production of the hepatocyte-stimulating activity for fibrinogen biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a significant decrease of the production of OSM by LPS-activated monocytes. In situ activation of monocytes by cytokines in the vessel wall could also contribute to the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.
Vasse
M
M
DIFEMA, Medical University of Rouen., St Etienne du Rouvray, France.
Paysant
J
J
Soria
J
J
Collet
J P
JP
Vannier
J P
JP
Soria
C
C
D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects; D005340:Fibrinogen / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D053683:Oncostatin M; D010452:Peptide Biosynthesis; D010455:Peptides / Q000494:pharmacology; D012306:Risk; D013927:Thrombosis / Q000097:blood* / Q000453:epidemiology; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D005340:Fibrinogen