TNF-alpha suppresses IL-6 upregulation of protein S in HepG-2 hepatoma cells.
The pathogenesis of disseminated intravascular coagulation (DIC) has, in part, been attributed to the impairment of the natural anticoagulant protein C/protein S pathway. DIC, which frequently occurs during sepsis, has been linked to cytokines that can induce or modulate procoagulant activity. Three of these cytokines, IL-1 alpha, IL-6, and TNF-alpha have been reported to be increased in the early stages of sepsis. In the present study, we have stimulated HepG-2 hepatoma cell cultures with recombinant human IL-1 alpha, IL-6, TNF-alpha, and oncostatin M (OSM). The results demonstrated that TNF-alpha, and to a lesser degree, IL-1 alpha, could significantly suppress IL-6 upregulation of protein S, whereas the effects of OSM was only suppressed by the combination of IL-1 alpha and TNF-alpha. The combination of IL-1 alpha and TNF-alpha also suppressed protein S production below that of control or basal levels. These results indicate that IL-1 alpha and TNF-alpha may play important regulatory roles in coagulation.
Hooper
W C
WC
Hematologic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Ga 30333, USA.
Phillips
D J
DJ
Evatt
B L
BL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D017293:Protein S / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D000970:Antineoplastic Agents; D016207:Cytokines; D053683:Oncostatin M; D010455:Peptides; D017293:Protein S; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508351:OSM protein, human