Transforming growth factor-b 1 (TGF-b 1) produced by in ltrating macrophage s plays a role in brotic disorders through the induction of myobroblasts. To explore possible mechanisms by which TGF-b 1 may act in this context, we investigated effects of TGF-b 1 on macrophage-like (HS-P) and myo broblastic (MT-9) cells, two novel cell lines developed by us. Immunocytochemicall y, the addition of TGF-b 1 (0, 0.1, 0.5, and 1.0 ng/ml) dose-dependentl y suppressed the expressions of antigens recognized by macrophage /histiocyte-speci c antibodies (ED1 and ED2) in HS-P cells, whereas the addition concomitantly increased the number of anti-a -smooth muscle actin antibody-positive myo broblastic cells, suggesting a possible phenotypica l modulation of macrophages into myo broblasts in the brotic lesions. By contrast, MT-9 cells did not show such immunophenotypica l changes following TGF-b 1 addition. DNA synthesis, measured by tritiated thymidine-incorporation , was inhibited in a dose-dependen t manner in MT-9 cells by TGF-b 1 addition (0, 0.1, 0.2, 0.5, 1.0, 5, and 10 ng/ml), but that in HS-P cells was unchanged . Northern blot analysis revealed that expressions of cell cycle-related early genes, c-jun and c-myc, were increased in HS-P cells after TGF-b 1 (1 ng/ml) addition, with c-jun showing peak expression prior to c-myc. By contrast, the peak expressions of c-jun and c-myc were delayed in TGF-b 1 (1 ng/ml)-added MT-9 cells, and their levels were less in MT-9 cells than in HS-P cells. Furthermore, TGF-b 1 (1 and 10 ng/ml) induced DNA laddering in MT-9 cells, but did not in HS-P cells. Based on these ndings, it was speculated that TGF-b 1 could have induced G1 arrest in cell cycle and apoptosis in MT-9 cells. The present study showed that there were signi cant differences in the effects of TGF-b 1 between macrophage-like HS-P cells and myo broblastic MT-9 cells, presumably depending on divergent susceptibilities to TGF-b 1 between both cell types. Because such cell types are key cells in the brogenesis, HS-P and MT-9 might be useful models for investigating the pathogenesi s of brosis in vitro.
