title: Bacterial endotoxin regulation of cytokine receptors on murine bone marrow cells: in vivo and in vitro study.
abstract: Bacterial endotoxin (LPS) modulation of CSF-1, granulocyte-macrophage (GM)-CSF, G-CSF, IL-1, TNF, and Kit Ligand receptors on murine bone marrow cells (BMC) in vivo and in vitro was investigated. In vivo LPS reduced the binding of hrIL-1 (> 90%), mrTNF (> 62%), mrGM-CSF (> 42%) and hrG-CSF (> 91%) to BMC within 2 h, but elevated IL-1 binding (> 8.4-fold) between 8 to 48 h. In vitro, LPS decreased G-CSF and IL-1 binding after 8 h yet increased TNF binding in a dose-dependent manner, suggesting that in vivo, the LPS up-regulation of IL-1 binding to BMC was indirect. Because in vivo LPS elevated the levels of TNF, IL-6, GM-CSF, and glucocorticoids, we further examined GM-CSF and TNF modulation of cytokine receptors on BMC in vivo. In vivo, TNF decreased the binding of TNF (> 88%), G-CSF (> 89%), and IL-1 (> 73%) within 30 min, but increased IL-1 binding (> 4.8-fold) after 10 h. In contrast, in vitro TNF decreased IL-1 binding after 8 h, implying that in vivo TNF up-regulation of Il-1 binding to BMC was also due to an indirect mechanism. However, GM-CSF increased IL-1 binding to BMC both in vivo and in vitro after 8 h. Further studies showed that in vitro GM-CSF and dexamethasone synergistically increased IL-1 binding to BMC in a time- and dose-dependent manner. This synergistic modulation depended on synthesis of protein and mRNA, and was due to an increase in receptor number rather than an increase in receptor affinity. Because in vivo, LPS and LPS-induced cytokines (IL-1 and TNF) elicited the secretion of glucocorticoid and CSF activities, our results revealed a mechanism for LPS up-modulation of IL-1R on BMC in vivo.
authors.affiliation: James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: J H
authors.initials: JH
authors.lastname: Shieh
authors.forename: R H
authors.initials: RH
authors.lastname: Peterson
authors.forename: M A
authors.initials: MA
authors.lastname: Moore
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018121:Receptors, Cytokine / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor