Inhibition of interleukin-11 by interferon-alpha in human bone marrow stromal cells.
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.
Aman
M J
MJ
III Department of Internal Medicine, Johannes-Gutenberg-University, School of Medicine, Mainz, Germany.
Bug
G
G
Aulitzky
W E
WE
Huber
C
C
Peschel
C
C
D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D017370:Interleukin-11 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007375:Interleukin-1; D017370:Interleukin-11; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide