TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812.
The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.
Nilsson
G
G
Department of Pathology, University of Uppsala, Sweden.
Carlsson
M
M
Jones
I
I
Ahlstedt
S
S
Matsson
P
P
Nilsson
K
K
D001491:Basophils / Q000166:cytology*; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D006632:Histamine / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute / Q000276:immunology; D018123:Receptors, Interleukin / Q000032:analysis; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
D003470:Culture Media; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine