Abstract
The effect of 17β-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor α (TNFα). Addition of 17β-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17α-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17β-estradiol. 17β-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
| Original language | English |
|---|---|
| Pages (from-to) | 883-891 |
| Number of pages | 9 |
| Journal | Journal of Clinical Investigation |
| Volume | 89 |
| Issue number | 3 |
| State | Published - 1992 |
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Keywords
- Interleukin-1
- Marrow stroma
- Osteoclast
- Osteoporosis
- Tumor necrosis factor
ASJC Scopus subject areas
- Medicine(all)
Cite this
17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro : A potential mechanism for the antiosteoporotic effect of estrogens. / Girasole, Giuseppe; Jilka, Robert L.; Passeri, Giovanni; Boswell, H.; Boder, George; Williams, Daniel C.; Manolagas, Stavros C.
In: Journal of Clinical Investigation, Vol. 89, No. 3, 1992, p. 883-891.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro
T2 - A potential mechanism for the antiosteoporotic effect of estrogens
AU - Girasole, Giuseppe
AU - Jilka, Robert L.
AU - Passeri, Giovanni
AU - Boswell, H.
AU - Boder, George
AU - Williams, Daniel C.
AU - Manolagas, Stavros C.
PY - 1992
Y1 - 1992
N2 - The effect of 17β-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor α (TNFα). Addition of 17β-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17α-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17β-estradiol. 17β-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
AB - The effect of 17β-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor α (TNFα). Addition of 17β-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17α-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17β-estradiol. 17β-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
KW - Interleukin-1
KW - Marrow stroma
KW - Osteoclast
KW - Osteoporosis
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0026516415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026516415&partnerID=8YFLogxK
M3 - Article
VL - 89
SP - 883
EP - 891
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -