Differential Cytokine Regulation of PAI-1 Gene Expression Between Human Umbilical and Subcutaneous Fat-Derived Microvascular Endothelial Cells

Plasminogen activator inhibitor-1 (PAI-1) levels are regulated by inflammatory cytokines. In human umbilical vein endothelial cells (HUVECs), PAI-1 expression is regulated by interleukin-1β (IL1), transforming growth factor-β (TGF) and tumor necrosis factor-α (TNF), but not by interleukin-6 (IL6). TNF and epidermal growth factor (EGF) increase both PAI-1 as well as IL6 expression in human subcutaneous fat cell-derived human microvascular endothelial cells (SF-MECs). We investigated further the potential for differential response opf PAI-1 production by these diverse endothelial cells to IL6, ILl, and TNF. Treatment of SF-MECs with recombinant human IL6 and TNF (rhIL6 & rTNF) caused a maximum 3- to 3.4-fold increase in PAI-1 levels whereas rIL1 slightly decreased PAI-1 levels. In contrast, HUVECs showed increased production of PAL1 by rIL1 and rTNF but not by rhIL6. rhIL6-induced-PAI-1 production in SF-MECs was significant by 6 hr of treatment, and was specifically inhibited to basal levels by neutralizing...