FIGURE 3.
p425 impairs MIF-mediated production of IL-6, IL-8, and MMP-3 and inhibition of p53-dependent apoptosis. A, inhibition of rhMIF-induced IL-6 (left panel) and IL-8 (right panel) production in human foreskin fibroblast cells in the presence of p425 (white), ISO-1 (stipple), and anti-MIF antibody (black). IL-6 and IL-8 levels in the culture medium were determined by ELISA, and the percent inhibition was calculated with respect to a no-inhibitor control. Dose-dependent inhibition of rhMIF-induced IL-6 (B) and IL-8 (C) production in the presence of p425 and ISO-1. D, inhibition of MMP-3 production in the presence of p425 and ISO-1 in primary human synovial fibroblast cells. MMP-3 levels in the culture medium were determined by ELISA, and the percent inhibition was calculated with respect to a no-inhibitor control. E, p425 impairs the ability of rhMIF to inhibit p53-dependent apoptosis. HeLa cells were exposed to camptothecin (CAM) and then treated with rhMIF or rhMIF plus p425. Apoptosis was measured by ELISA. The plot shows the level of apoptosis in untreated (CAM), treated with rhMIF alone (CAM+MIF) and rhMIF in the presence of 2, 10, and 50 μm p425. F, p425 does not cause significant cytotoxicity in human foreskin fibroblast cells.
