ACTIVITY OF INTERFERON-ALPHA, INTERLEUKIN-6 AND INSULIN IN THE REGULATION OF DIFFERENTIATION IN A549 ALVEOLAR CARCINOMA-CELLS

The differentiation of A549, a human tumour cell line from type II pne umocytes, can be induced by a crude fibroblast-derived factor (FDF) is olated from the conditioned medium of glucocorticoid-treated lung fibr oblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of gro wth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-a lpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a hal f-life of 1 week. Transforming growth factor alpha and beta, IL-1 alph a and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lun g fibroblast-conditioned medium it seems an unlikely candidate for FDF . Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the abs ence of DX. This suggests that differentiation-inducing activity may b e present in several paracrine factors, but that so far a candidate fo r FDF has not been identified.