Regulation of interleukin-4 receptors on murine myeloid progenitor cells by interleukin-6.
Interleukin-4 (IL-4) is a T-cell-derived cytokine that regulates induction of proliferation of resting B cells and acts on various other immunocompetent cells, such as monocytes/macrophages and mast cells, as well as hematopoietic progenitor cells. On hematopoietic progenitor cells, cooperation with another cytokine (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, IL-3, or IL-6) is required to render the cells responsive to IL-4. The present study was undertaken to determine if such an interaction entails induction of IL-4 receptor (IL-4R) expression. Using the murine myeloid leukemia M1 cell line and mature, bone marrow (BM)-derived macrophages, we investigated whether IL-4R expression can be induced during differentiation. We detected no high-affinity IL-4R on the surface of either cell, but with exposure to IL-6 a significant induction of IL-4R was measured on both cell types by fluorescence-activated cell sorter analysis. This increase in IL-4R was first noted 6 hours after exposure of the cells to IL-6 and continued to increase up to 48 hours. By RNase protection analysis we found that the expression of IL-4R mRNA also appeared within 6 hours, continuing to increase up to 48 hours. Nuclear run-on assays showed that this increase in steady-state level of IL-4R mRNA results from a transcriptional activation of the IL-4R gene. These data suggest that regulation of IL-4R expression by IL-6 is under transcriptional control.
Feldman
G M
GM
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
Ruhl
S
S
Bickel
M
M
Finbloom
D S
DS
Pluznik
D H
DH
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen