The Production of Heparin Cofactor li Is Not Regulated by Inflammatory Cytokines in Human Hepatoma Cells: Comparison with Plasminogen Activator Inhibitor Type-1
Chisato Kolke
1
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
2
Third Department of Internal Medicine, Faculty of Medicine, Yamagata University, Yamagata, Japan
,
Yumiko Hayakawa
1
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
,
Kenji Niiya
1
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
,
Nobuo Sakuragawa
1
The Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
,
Hideo Sasaki
2
Third Department of Internal Medicine, Faculty of Medicine, Yamagata University, Yamagata, Japan
Using the Northern blot technique, we screened 6 human hepatoma cell lines to investigate the regulation mechanism of heparin cofactor II (HCII) biosynthesis. We found that HuH-7 and Hep G2 cells constitutively expressed the HC II gene. In conditioned medium, HuH-7 cells constantly produced HC II that was functionally active and formed a complex with thrombin in the presence of dermatan sulfate. HC II is thought be an acute phase reactant, and, therefore, we examined the effects of the major inflammatory cytokines, IL-6, IL-1β, and TNF-α, on the regulation of HC II production in HuH-7 and Hep G2 cells. In HuH-7 cells, the antigen and mRNA levels of plasminogen activator inhibitor type-1 (PAI-1), an acute phase protein produced by hepa-tocytes, were increased in response to stimulation with either IL-6 or IL-1 (3 or both, but HC II antigen and mRNA levels were not changed by the same stimulation. Even when Hep G2 cells were treated with a combination of three cytokines, IL-6, IL-1β, and TNF-α, HC II antigen and mRNA levels were not changed; however, PAI-1 antigen and mRNA levels were clearly increased. These results suggest that the production of HC II in hepatoma cells is not regulated by the major inflammatory mediators, IL-6, IL-iβ, and TNF-α.
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