Fatty acids differentially modify the expression of urokinase type plasminogen activator receptor in monocytes

The urokinase plasminogen activator system with its receptor uPAR contributes to the migratory potential of macrophages, a key event in atherosclerosis. We here investigated whether free fatty acids (FFA) modify the expression for uPAR in the PMA-differentiated human monocyte/macrophage-like cell line U937. Two hundred micromolar palmitate induced a threefold increase of the uPAR mRNA expression. Although the mono- and polyunsaturated fatty acids oleate and linoleate also stimulated uPAR expression, oleate had a significantly lower effect than palmitate. The observed effects were time and dose dependent. Inhibition of PKC-and ERK-pathways resulted in a strong down-regulation of basal uPAR expression whereas the FFA induced up-regulation remained unchanged. In contrast, FFA induced uPAR up-regulation was abolished by the specific inhibition of p38 MAPK. In conclusion we demonstrate that uPAR expression in human monocytes/macrophages is differentially stimulated by FFA. These effects are partially mediated by the p38 MAP-kinase signaling pathway.