The synthesis of alpha 2-macroglobulin by rat mammary myoepithelial cells is regulated by synergism between glucocorticoids and cytokines.

Addition of hydrocortisone to the rat mammary gland myoepithelial cell line, G4.2.3, induces the synthesis and secretion of alpha 2-macroglobulin. Interleukin-1 beta, interleukin-6 and transforming growth factor-beta synergize with hydrocortisone, increasing the synthesis of alpha 2-macroglobulin 2- to 4-fold, although they have no effect in the absence of hydrocortisone. Interleukin-6 is the most potent inducer having an optimum concentration of 1 ng/ml. Interleukin-6, unlike interleukin-1 beta or transforming growth factor-beta, decreases the lag phase from 10 h to 4 h before alpha 2-macroglobulin synthesis is induced by hydrocortisone. These results suggest that the mechanism of activation of transcription of the alpha 2-macroglobulin gene in mammary myoepithelial cells might differ from that operating in hepatic cells.