| Abstract: |
Human recombinant granulocyte CSF (G-CSF) modulation of cytokine receptors on murine bone marrow cells (BMC) in vivo and in vitro was investigated. In vivo, G-CSF reduced 125I-G-CSF binding to BMC by >95% within 30 min, with return to base line after 48 h. Human rCSF-1 binding was reduced >85% after 30 min and failed to recover even after 48 h. Murine rTNF-α or recombinant granulocyte/ macrophage CSF binding was not significantly altered. However, human rIL-1α binding increased >1.5-fold after 3 h, was elevated >5-fold between 6 and 12 h, and declined to base line after 48 h. In vitro, G-CSF induced a >1.5-fold increase in IL-1 binding to BMC after 8 h, suggesting that up-modulation of IL-1 binding in vivo required G-CSF and other influences. Further studies indicated that BMC responded to glucocorticoids and G-CSF with a synergistic increase of IL-1 binding. This synergistic IL-1R modulation was a time- and dose-dependent process and was inhibited by cycloheximide or actinomycin D in a dose-dependent manner. Binding studies further revealed that the synergistic stimulation of IL-1R expression on BMC was probably due to increased receptor number, rather than increased receptor affinity. In addition, this phenomenon was also observed in other hematopoietic cells. Our results demonstrated that G-CSF was capable of stimulating IL-1R expression on BMC both in vivo and in vitro and G-CSF in combination with glucocorticoids synergistically up-modulated IL-1 binding to BMC in vitro. Inasmuch as IL-1 induces the secretion of G-CSF and glucocorticoids in vivo, this synergistic induction may play an important, as yet unknown, role in the inflammatory cascade. |
| Keywords: |
controlled study; nonhuman; animal cell; mouse; animal; mice; bone marrow; dexamethasone; tumor cells, cultured; mice, inbred strains; cytokine; receptors, interleukin-1; hematopoietic stem cells; dactinomycin; bone marrow cell; up-regulation; granulocyte colony-stimulating factor; granulocyte; in vitro; tumor necrosis factor; receptors, immunologic; receptors, cell surface; interleukin-1; receptors, tumor necrosis factor; steroids; cycloheximide; cell receptor; colony stimulating factor; interleukin 1 receptor; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; receptors, colony-stimulating factor
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