TY - JOUR
T1 - Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors
AU - Kassem, Moustapha
AU - Harris, Steven A.
AU - Spelsberg, Thomas C.
AU - Riggs, B. Lawrence
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1996/2
Y1 - 1996/2
N2 - Some studies suggest that estrogen acts on bone by decreasing the production of interleukin-6 (IL-6), a cytokine that increases bone resorption, by osteoblasts or bone marrow cells. However, other studies have not confirmed this, possibly because of a low and variable number of estrogen receptors (ER) in the model systems used. Thus, we employed a recently developed human fetal osteoblast cell line with high levels of ER. Treatment (n = 4 experiments) with 0.01 to 10 nM of 17β-estradiol had no effect on the constitutive production of IL-6. However, stimulated production, induced by treatment with IL-1β plus tumor necrosis factor-α (TNF-α), was reduced in a dose-dependent manner to 74 ± 3% (mean ± SEM) of control (p < 0.01). This response was blocked by cotreatment with the type II antiestrogeu ICI 182,780. Treatment with hydrocortisone (1 μM), a known inhibitor of IL-6 production in many cell types, reduced IL-6 production to 17 ± 1% of control (p < 0.001). As assessed by Northern analysis, treatment (n = 3 experiments) with 0.01-10 nM of 17β-estradiol decreased steady-state levels of IL-6 mRNA in a dose-dependent manner. These data support the hypothesis that at least part of the antiresorptive action of estrogen in humans is mediated by decreased production of IL-6 by osteoblastic cells.
AB - Some studies suggest that estrogen acts on bone by decreasing the production of interleukin-6 (IL-6), a cytokine that increases bone resorption, by osteoblasts or bone marrow cells. However, other studies have not confirmed this, possibly because of a low and variable number of estrogen receptors (ER) in the model systems used. Thus, we employed a recently developed human fetal osteoblast cell line with high levels of ER. Treatment (n = 4 experiments) with 0.01 to 10 nM of 17β-estradiol had no effect on the constitutive production of IL-6. However, stimulated production, induced by treatment with IL-1β plus tumor necrosis factor-α (TNF-α), was reduced in a dose-dependent manner to 74 ± 3% (mean ± SEM) of control (p < 0.01). This response was blocked by cotreatment with the type II antiestrogeu ICI 182,780. Treatment with hydrocortisone (1 μM), a known inhibitor of IL-6 production in many cell types, reduced IL-6 production to 17 ± 1% of control (p < 0.001). As assessed by Northern analysis, treatment (n = 3 experiments) with 0.01-10 nM of 17β-estradiol decreased steady-state levels of IL-6 mRNA in a dose-dependent manner. These data support the hypothesis that at least part of the antiresorptive action of estrogen in humans is mediated by decreased production of IL-6 by osteoblastic cells.
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U2 - 10.1002/jbmr.5650110208
DO - 10.1002/jbmr.5650110208
M3 - Article
C2 - 8822343
AN - SCOPUS:0030020568
SN - 0884-0431
VL - 11
SP - 193
EP - 199
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 2
ER -