Transforming growth factor‐β1 stimulates macrophage urokinase expression and release of matrix‐bound basic fibroblast growth factor
- 1 June 1993
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 155 (3), 595-605
- https://doi.org/10.1002/jcp.1041550317
Abstract
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.Keywords
This publication has 64 references indexed in Scilit:
- Interactions between type 1 plasminogen activator inhibitor, extracellular matrix and vitronectinCell Differentiation and Development, 1990
- The Transforming Growth Factor-beta FamilyAnnual Review of Cell Biology, 1990
- TGF-β stimulation and inhibition of cell proliferation: New mechanistic insightsCell, 1990
- The effects of the protein kinase C inhibitors staurosporine and H7 on the IgE dependent mediator release from RBL 2H3 cellsInflammation Research, 1990
- Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity.The Journal of cell biology, 1990
- Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta.The Journal of cell biology, 1989
- Heparin stimulation of plasminogen activator secretion by macrophage‐like cell line raw264.7: Role of the scavenger receptorJournal of Cellular Physiology, 1989
- Recent developments in the cell biology of basic fibroblast growth factor.The Journal of cell biology, 1989
- Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex.The Journal of cell biology, 1989
- Macrophage plasminogen activator: induction by concanavalin A and phorbol myristate acetateCell, 1977