Plasminogen activator inhibitor (PAI)-1 promotes development of asthma. PAI-1 mRNA and protein are markedly induced in activated mast cells (MCs), a major effector cell type in asthma. However, regulatory mechanisms of PAI-1 transcription in MCs are unknown. We present first evidence that PAI-1 is transcriptionally regulated in human MCs (hMCs). In addition to three enhancer regions, we demonstrated that the E-box at -566 bp to -561 bp is the negative regulatory element, and the specific and constitutive binding of the upstream stimulating factor-1 to this E-box is the key mechanism of the negative regulation of PAI-1 expression in hMCs.
- Human mast cells (hMCs)
- Plasminogen activator inhibitor-1 (PAI-1)
- Upstream stimulating factor-1 (USF-1)