Hemin or butyrate increases constitutive erythropoietin formation by mouse erythroleukemia cell lines

The murine erythroleukemic cell lines NN10 and IW32 secrete erythropoietin (Epo) constitutively. Although both cell lines have Epo receptors (Epo-R), they do not respond to external Epo to undergo erythroid differentiation. In both cell lines, hemoglobin synthesis can be induced by hemin or butyrate. We report here on the effects of these two inducers on Epo production by the same cell lines. Both hemin and butyrate caused a three- to five-fold increase in Epo secretion on a percell basis. The effects were dose- and time-dependent, as was found previously for hemoglobin synthesis. The mechanism of the effect on Epo secretion is posttranscriptional, since the steady-state level of Epo mRNA was not altered by the inducers.