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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

IL-1beta down-regulates tissue-type plasminogen activator by up-regulating low-density lipoprotein receptor-related protein in AML 12 cells.

Interleukin-1 (IL-1) regulation of tPA in hepatocytes was studied in mouse hepatocyte line AML12. IL-1 induced transient accumulation of tPA mRNA as high as threefold by 2 h after the start of treatment. The cytokine also induced the mRNA for serum amyloid A, a typical acute-phase protein in mice, with more sustained kinetics in a time-dependent manner. In contrast to the induction of mRNA, tPA activity and protein levels in the harvested medium were dramatically diminished by IL-1. IL-1 stimulated the uptake of (125)I-tPA by AML 12. This uptake was inhibited by 39-kDa receptor-associated protein (RAP), but not by the sugar mannan. These results revealed that low-density lipoprotein receptor-related protein ( LRP), which is known to be a receptor for tPA and to be blocked by RAP, was up-regulated by IL-1. We also demonstrated, for the first time, that IL-1 transiently increased the mRNA level of LRP threefold by 30 min after the start of IL-1 treatment of AML 12. The receptor-mediated endocytosis of tPA by hepatocytes may thus play a crucial role in the down-regulation of fibrinolysis during the acute-phase response.[1]

References

  1. IL-1beta down-regulates tissue-type plasminogen activator by up-regulating low-density lipoprotein receptor-related protein in AML 12 cells. Noguchi, T., Noguchi, M., Masubuchi, H., Seki, T., Ariga, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
 
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