Differential expression of transforming growth factor-β1, -β2, and -β3 by glioblastoma cells, astrocytes, and microglia

The type β transforming growth factors (TGF) are potent regulators of the growth and functions of lymphocytes and macrophages. Recently the human glioblastoma cell line 308 was shown to produce TGF-β2. The relevance of this finding was evaluated further by comparing human glioblastoma cells with their nontransformed animal counterpart, astrocytes, with regard to the production of the three TGF-β isoforms observed so far in mammals. In this report astrocytes are demonstrated to secrete also TGF-β2 and to express TGF-β1, -β2, and -β3 mRNA in vitro. In contrast, cultured murine brain macrophages release TGF-β1 and are positive for TGF-β1 mRNA only. Glia cell-derived TGF-β1 and -β2 are detected in latent form whereas both latent and active TGF-β are identified in the supernatant of three human glioblastoma cell lines tested. These cell lines, however, show heterogeneity in regard to the isoform of TGF-β expressed but share with astrocytes the inability to release TGF-β3. Provided production and activation of latent TGF-β occur in vivo, astrocytes and microglia may then be expected to exert regulatory influences on immune mediated diseases of the central nervous system.