IFN-beta selectively down-regulates transferrin receptor expression in human peripheral blood macrophages by a post-translational mechanism.
We evaluated the effect of IFN-beta on the expression of transferrin receptor (TfR) during the in vitro differentiation of peripheral blood monocytes to macrophages. IFN-beta exerted a strong inhibitory effect on the expression of TfR. As little as 0.1 IU/ml was sufficient to induce a 40% reduction of transferrin (Tf) binding sites on 7-day cultured macrophages. Scatchard plot analysis revealed that this impaired Tf binding in IFN-beta-treated macrophages was not due to a decreased affinity of the TfR for its ligand but to a reduction in the number of cell surface TfR. IFN-gamma did not exert any significant effect on the expression of TfR, even though it was capable of partially reverting the inhibitory effect of the IFN-beta on Tf binding. To understand the mechanism by which IFN-beta inhibited TfR expression, we examined the expression of TfR mRNA, 125I-Tf binding to detergent-solubilized cells, and TfR cellular distribution. The results of these experiments showed that IFN-beta caused neither a significant alteration of the expression of TfR mRNA nor a decrease of the total content of TfR molecules. Moreover, immunofluorescence analysis of TfR localization indicated that TfR was clustered in an intracellular compartment in IFN-beta-treated macrophages. These data demonstrate that IFN-beta is capable of dramatically down-modulating TfR in macrophages by post-translational mechanisms (i.e., by sequestering this receptor in intracellular compartments).
Testa
U
U
Department of Hematology and Oncology, Istituto Superiore di Sanità, Rome, Italy.
Conti
L
L
Sposi
N M
NM
Varano
B
B
Tritarelli
E
E
Malorni
W
W
Samoggia
P
P
Rainaldi
G
G
Peschle
C
C
Belardelli
F
F
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016899:Interferon-beta / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D007457:Iodine Radioisotopes; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D009000:Monocytes / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011990:Receptors, Transferrin / Q000235:genetics / Q000502:physiology*; D014168:Transferrin / Q000378:metabolism
D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin; D014168:Transferrin; D016899:Interferon-beta; D007371:Interferon-gamma