Abstract
Administration of highly purified preparations of murine interferon (IFN)-alpha 1, -alpha 4, -alpha 6, or -beta to Friend leukemia cells induced to differentiate by dimethyl sulfoxide leads to a 100% increase of benzidine-positive (B+) cells. Different efficiencies for the two IFN species have been observed; a 10-fold higher dose of IFN-alpha is needed for stimulation of hemoglobin production and inhibition of cell growth as compared with IFN-beta. Both species of IFN induce a substantial increase in heme, hemoglobin, and transferrin receptor levels. In vitro run-on transcription assays indicate that IFN-beta moderately stimulates transcription of the alpha-globin gene but not the transferrin receptor gene. It is postulated that IFN induces the enhancing effect on differentiation via a marked increase of heme synthesis and number of transferrin receptors, which in turn leads to an enhancement of globin chain synthesis. In this regard, the negative feedback reported in a variety of other cell types for the regulation of transferrin receptor expression by heme does not seem to be operative in maturing Friend erythroleukemia cells, which present evidence for a positive mechanism.
Highlights
Angela BattistiniS, GiovannaMarzialiS, RobertoAlbertinit, Daniela Habetswallnerll, Daniela Bulgarinill, Eliana M
IFN-B moderately stimulates transcription of the a- The present study reports the effects of IFN-a and -/3 on globin gene but not the transferrin receptor gene
IFN is comprised of a family of proteins that act ina. These results support existing data that indicate that IFN species-specific manner, eliciting a wide range of biological stimulates Hb production and transferrinreceptor expression effects, including those on cell differentiation, which, at presin MezSO-inducedFLC
Summary
Angela BattistiniS, GiovannaMarzialiS, RobertoAlbertinit, Daniela Habetswallnerll, Daniela Bulgarinill, Eliana M. To estimate the number of transferrin receptors, binding assays mixture was shaken vigorously and heated immediately for 30 min at were performed as described above except that thecells were exposed. The hybridization was and incubation for 10 min at 4 "C, the transferrin receptor complex carried out with globin cDNA clones designated pCR, ocMG1Oand was precipitated by adding 1 ml of mM citrate buffer (pH 5.5). The amount of free '251-transferrin precipitated was estimated by omittingthe cell extract from the incubation mixture and never exceeded 3% of the specific binding. Filters were washed twice for 15 min in 2 adult mouse heme-free globin chains, prepared from Hb [26], were 0.1 X SSC and 0.1% SDS at room temperature andthen for an added as carrier to the supernatanwtith 1ml of acid acetone.
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