Transforming growth factor‐β1 stimulates macrophage urokinase expression and release of matrix‐bound basic fibroblast growth factor
Journal of Cellular Physiology
Macrophage expression of urokinase‐type plasminogen activator (uPA) appears to play a role in their release of matrix‐bound basic fibroblast growth factor (bFGF) and transforming growth factor‐β (TGF‐β). In experiments reported here, we have examined the potential regulatory effects of bFGF and TGF‐β1 on macrophage uPA expression. TGF‐β1 stimulated in a dose‐ and time‐dependent manner the expression of secreted membrane and intracellular uPA activities by a macrophage cell line (RAW264.7). When examined at similar concentrations, bFGF had little effect, and interleukin‐1α, tumor necrosis factor‐α, and monocyte colony stimulating factor had no effect on macrophage uPA expression. Exposure of macrophages to TGF‐β1 led to a rapid and sustained increase in the steady‐state levels of uPA mRNA that was independent of de novo protein synthesis and was completely inhibited by actinomycin D. However, the TGF‐β1‐induced increase in uPA mRNA was largely unaffected by subsequent incubation of cells with actinomycin D. The protein kinase C inhibitior H7 markedly reduced the ability of TGF‐β1 to stimulate expression of uPA activity. Likewise, okadaic acid and microcystin, inhibitors of serine/threonine phosphatases, potentiated the ability of TGF‐β1 to upregulate macrophage uPA expression. TGF‐β1 primed cells converted nearly all added plasminogen to plasmin and expressed sixfold more membrane‐bound plasmin than control cells. Preincubation of TGF‐β1 with either serum or methylamine‐modified α2‐macroglobulin did not affect its ability to induce macrophage uPA expression. When control and TGF‐β1‐primed macrophages were cultured on matrices containing bound125I‐bFGF, their release of 125I‐bFGF was increased five and tenfold, respectively, in the presence of plasminogen. The ability of TGF‐β to induce macrophage uPA expression and the plasmin‐dependent release of matrix‐bound bFGF may provide an indirect mechanism by which TGF‐β stimulates angiogenesis. © 1993 Wiley‐Liss, Inc. Copyright © 1993 Wiley‐Liss, Inc.
Falcone, D., McCaffrey, T., Haimovitz‐Friedman, A., & Garcia, M. (1993). Transforming growth factor‐β1 stimulates macrophage urokinase expression and release of matrix‐bound basic fibroblast growth factor. Journal of Cellular Physiology, 155 (3). http://dx.doi.org/10.1002/jcp.1041550317