he 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.
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, G.; Jilka, R. L.; Passeri, Giovanni; Boswell, S.; Boder, G.; Williams, D. C.; Manolagas, S. C.. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - 89:3(1992), pp. 883-891. [10.1172/JCI115668]
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 G.;PASSERI Giovanni;
1992-01-01
Abstract
he 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.