| First Author | Seki T | Year | 1996 |
| Journal | J Cell Physiol | Volume | 168 |
| Issue | 3 | Pages | 648-56 |
| PubMed ID | 8816919 | Mgi Jnum | J:36132 |
| Mgi Id | MGI:83573 | Doi | 10.1002/(SICI)1097-4652(199609)168:3<648::AID-JCP17>3.0.CO;2-V |
| Citation | Seki T, et al. (1996) Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12. J Cell Physiol 168(3):648-56 |
| abstractText | Type-1 plasminogen activator inhibitor (PAI-1), the major regulator of fibrinolysis, is an important component of the acute phase (AP) response, the coordinated systemic reaction of an organism to tissue injury. As part of a combined in vivo and in vitro study of AP regulation of PAI-1 gene expression in murine hepatocytes, we have characterized the cytokine regulation of PAI-1 gene expression in AML 12 cells, an established line of normal hepatocytes derived from an adult transgenic mouse overexpressing transforming growth factor alpha. Interleukin (IL)-1 caused a rapid and transient 4-fold increase in PAI-1 mRNA that was maximal at 1 h. Half-maximal induction by IL-1 was obtained at 50 U/ml and maximal effects were seen at approximately 500 U/ml. Tumor necrosis factor alpha induced PAI-1 mRNA accumulation with the same magnitude and time course as IL-1, and was not additive with IL-1. IL-6 and dexamethasone alone had no effect on PAI-1 mRNA accumulation and did not enhance the effect of IL-1. Transforming growth factor beta caused a sustained 5- to 7-fold increase in the accumulation of PAI-1 mRNA that was maximal after 2 to 4 h. The IL-1 induction of PAI-1 was inhibited by actinomycin D, but not by cycloheximide. Nuclear run-on studies demonstrated that IL-1 induced a rapid and transient increase in PAI-1 gene transcription that was maximal at 30 min. IL-1 did not stabilize PAI-1 mRNA, and might, in fact, accelerate its rate of decay. These data demonstrate that IL-1, a potent mediator of AP response, induces the accumulation of PAI-1 mRNA in murine hepatocytes, at least in part, by rapidly and transiently increasing the rate of transcription of the PAI-1 gene. |
