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\nHypoxia-induced extracellular matrix metalloproteinase inducer (EMMPRIN) is a glycoprotein that increases the expression and activity of the matrix metalloproteinase MMP-9. A previous report demonstrated that hypoxia increases interferon-gamma (IFNgamma) expression in human umbilical vein endothelial cells (HUVECs). We asked whether hypoxia might also increase the expression of EMMPRIN and whether IFNgamma might mediate such a response. EMMPRIN expression was increased in hypoxic HUVECs. Pretreatment of these cells with IFNgamma resulted in a dose-dependent increase in EMMPRIN expression, which was protein kinase C (PKC) dependent and was regulated by the transcription factor nuclear factor kappaB (NFkappaB). The time course of EMMPRIN and IFNgamma expression revealed that hypoxia induced the expression of EMMPRIN at the transcriptional level, which preceded the increased expression of IFNgamma. Similar results were obtained with MMP-9 expression. The EMMPRIN promoter contains two NFkappaB sites that contain an IFNgamma-response element (IRF-1).
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