Regulation of interleukin-4 receptors on murine myeloid progenitor cells by interleukin-6

Blood. 1991 Oct 1;78(7):1678-84.

Abstract

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.

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Cell Differentiation
  • Gene Expression Regulation
  • Hematopoietic Stem Cells / metabolism*
  • Interleukin-6 / pharmacology*
  • Leukemia, Myeloid / metabolism*
  • Macrophages / metabolism
  • Mice
  • RNA, Messenger / genetics
  • Receptors, Interleukin-4
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin-4
  • Receptors, Mitogen