Estrogen inhibits interleukin-1beta-induced interleukin-6 production by human osteoblast-like cells.
Estrogen supplements are the primary pharmacologic intervention therapy to prevent and treat loss of bone mass (osteoporosis) in postmenopausal women. Furthermore, at sites of local inflammation near bone, estrogen-deficient women are significantly more susceptible to bone loss than are estrogen-sufficient women. In the present study, we investigate whether estrogen modulates osteoblast (MG-63) production of interleukin-6 (IL-6), an osteoclast recruitment and differentiation of cytokine, in the presence of the proinflammatory cytokine, IL-1beta. Using enzyme-linked immunosorbent assay (ELISA), we demonstrate that IL-1beta significantly enhances IL-6 secretion into culture supernatants in a dose-dependent and time-dependent manner. Using reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA respectively, we demonstrate further that levels of 17beta-estradiol (active metabolite of estrogen) > or = those found in serum of estrogen-sufficient women inhibit steady-state IL-6 mRNA levels as well as inhibit secretion of IL-6 into culture supernatants. One mechanism by which estrogen therapy preserves bone mass in areas of inflammation may be via inhibition of IL-1beta-stimulated obsteoblast-derived IL-6.
Bioregulation Laboratories, University of Nebraska Medical Center, Lincoln 68583-0750, USA. skoka@unmcvm.unmc.edu
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Koka
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Petro
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Reinhardt
D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000235:genetics*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D004958:Estradiol