Ethanol activates the interleukin-6 promoter in a human bone marrow stromal cell line.
Chronic ethanol consumption is associated with the development of osteoporosis. The pro-inflammatory cytokine interleukin-6 (IL-6) plays a role in the development of osteoporosis through stimulation of osteoclastic activity. We hypothesized that ethanol promotes osteoporosis, in part, by increasing IL-6 production in the bone microenvironment. Accordingly, we evaluated ethanol's effect on IL-6 production in the Saka human bone marrow stromal cell line and in the HOBIT human osteoblast-like cell line. We found that ethanol increased IL-6 protein levels in the culture supernatants from Saka, but not HOBIT, cells. In addition, we observed that ethanol increased steady-state IL-6 mRNA levels and activated an IL-6 promoter-driven reporter vector in Saka cells. We conclude that ethanol stimulates IL-6 expression in the Saka bone marrow stromal cell line by enhancing transcriptional activity of the IL-6 gene. Our findings support the contention that ethanol may contribute to the pathogenesis of osteoporosis, in part, by increasing IL-6 expression in the bone microenvironment.
Keller
E T
ET
Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, Norfolk, USA.
Zhang
J
J
Ershler
W B
WB
D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D010024:Osteoporosis / Q000139:chemically induced; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000187:drug effects
D015850:Interleukin-6; D012333:RNA, Messenger; D000431:Ethanol