IL-1 modulation of cytokine receptors on bone marrow cells. In vitro and in vivo studies.
We here investigated IL-1 modulation of cytokine receptors on murine bone marrow cells (BMC). In vivo, IL-1 treatment reduced greater than 88% of granulocyte-CSF, greater than 35% of TNF, and greater than 51% of granulocyte/macrophage-CSF binding to BMC after 3 h, and returned to base line after 48 h. However, IL-1 binding to BMC decreased greater than 30% after 30 min, dramatically increased greater than 9-fold between 6 and 10 h, and declined to base line after 48 h. In vitro incubation of BMC with IL-1 did not markedly alter IL-1 and granulocyte-CSF binding, suggesting that modulation of granulocyte-CSF and IL-1 binding to BMC by IL-1 in vivo is due to an indirect mechanism. Further in vitro studies showed that IL-1 binding to BMC was specifically induced by glucocorticoids rather than other steroids, and is a time- and dose-dependent process. IL-1 induced IL-1R up-regulation was suppressed by ketoconazole, cycloheximide, and actinomycin D in a dose-dependent manner. In addition, in vivo dexamethasone imitated the action of IL-1 in stimulating IL-1 binding to BMC and in inducing neutrophilia. Furthermore, IL-1 binding to BMC from sham mice 8 h after IL-1 administration was 2.5 times higher than that observed in adrenalectomized mice. Our results demonstrate, for the first time, that in vivo IL-1-induced increased IL-1 binding to BMC was due to an indirect mechanism, and glucocorticoids stimulated IL-1 binding to BMC in vivo and in vitro. Inasmuch as serum glucocorticoid levels can be elevated by IL-1 in vivo, these results reveal a novel mechanism by which IL-1 modulates its own receptors in vivo.
Shieh
J H
JH
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Peterson
R H
RH
Moore
M A
MA
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000187:drug effects; D011971:Receptors, Immunologic / Q000187:drug effects*; D017472:Receptors, Interleukin-1
D007375:Interleukin-1; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D016186:Receptor, Macrophage Colony-Stimulating Factor; D007654:Ketoconazole