Inhibition of interleukin-11 by interferon-alpha in human bone marrow stromal cells

Exp Hematol. 1996 Jul;24(8):863-7.

Abstract

Interleukin-11 (IL-11), which has been detected as a stromal cell-derived cytokine, regulates multiple steps of early hematopoiesis. Synthesis of IL-11 is induced by IL-1 and transforming growth factor-beta (TGF-beta) in stromal cells and fibroblasts, but the cytokines that inhibit its production remain to be defined. In the present study, we demonstrate that interferon-alpha (INF-alpha) downregulates IL-1-induced IL-11 in human bone marrow stromal cultures. In Northern blot experiments, expression of IL-11 mRNA was reduced in the presence of INF-alpha; this inhibiton was prevented by the addition of cycloheximide. In eight independent experiments, IL-1-stimulated production of IL-11 was significantly inhibited by INF-alpha (p = 0.0117) as measured in stromal cell supernatants by specific enzyme-linked immunosorbent assay (ELISA). Dose titration experiments revealed a dose-dependent inhibition already beginning at a dose level of 10 U/mL IFN. These results are in keeping with our previous observation defining an inhibitory role of INF-alpha in the production of hematopoietic growth factors produced by the bone marrow microenvironment.

MeSH terms

  • Bone Marrow / immunology
  • Bone Marrow Cells*
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology*
  • Interleukin-1 / pharmacology
  • Interleukin-11 / biosynthesis*
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Stromal Cells / drug effects
  • Stromal Cells / immunology*
  • Transcription, Genetic / drug effects*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-1
  • Interleukin-11
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Cycloheximide