| Abstract: |
Modulation of IL-1R on human neutrophils was investigated after in vitro treatment of cells with human recombinant (hr) granulocyte (G)-CSF, hrgranulocyte-macrophage (GM)-CSF, hrCSF-1, hrIL-1α, hrIL-2, hrIL-3, hrIL-4, hrIL-5, hrIL-6, hrIL-7, transforming growth factor-β1, or hrTNF-α. At 4°C, 125I-IL-1 binding was competed by IL-1 but not by other cytokines tested. At 37°C, GM-CSF, TNF-α, and IL-1 decreased 125I-IL-1 binding in a dose-dependent manner. Kinetic studies showed that GM-CSF reduced 〉45% IL-1 binding within 15 min but later (8 h) produced a 〉2-fold increase. In contrast, TNF decreased 〉85% IL-1 binding within 15 min with a recovery of 〉80% relative to that of control after 24 h. Scatchard analysis revealed that TNF or GM-CSF down-modulation of IL-1 binding was due to a decrease of IL-1R number. Further studies showed that dexamethasone and GM-CSF (or G-CSF) synergistically increased IL-1 binding after 8 h. This synergistic modulation was a cytokine dose- and time-dependent process, and was due to an increase in IL-1R numbers rather than a change in binding affinity. In addition, human bone marrow neutrophils, cord blood neutrophils, and several human hematopoietic cell lines (HL-60, U-937, and AML-193) responded to dexamethasone and GM-CSF (or G-CSF) with a superadditive increase in IL-1 binding. Because mammalian systems respond to bacterial endotoxins with secretion of TNF, IL-1, glucocorticoids, G-CSF and GM-CSF, our results shed additional light on this highly regulated cytokine network and revealed a novel role for GM-CSF. Copyright © 1993 by The American Association of Immunologists. |
| Keywords: |
leukemia; human cell; dose response; binding affinity; cells, cultured; transforming growth factor beta; granulocyte macrophage colony stimulating factor; dexamethasone; dose-response relationship, drug; tumor cells, cultured; cytokine; cytokines; tumor necrosis factor alpha; neutrophil; kinetics; receptors, interleukin-1; neutrophils; down regulation; recombinant granulocyte colony stimulating factor; receptor binding; tumor necrosis factor; interleukin-1; receptor upregulation; dose time effect relation; scatchard plot; granulocyte-macrophage colony-stimulating factor; cycloheximide; interleukin 1 receptor; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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