Regulation of Interleukin-6 expression in human osteoblastic cells in vitro

Summary

Interleukin-6 (IL-6) is a potent stimulator of bone resorption which has been demonstrated in a variety of in vivo and in vitro models. We investigated the regulation of IL-6 secretion in primary human osteoblastic cells (HOC) in vitro by cytokines known to play an important role in coupling bone formation to bone resorption. HOC were isolated from healthy adults who underwent selective orthopedic surgery and treated with cytokines released in the bone microenvironment during coupling i.e Interleukin-1 β (IL-lβ), Tumor Necrosis Factor a (TNFa), Transforming Growth Factor β 1 and 2 (TGFβ 1 and 2) and Endothelin-1 (ET-1). Furthermore, we determined whether systemically-acting steroid hormones of gonadal and adrenal origin as well as glucocorticoids affect the local regulation of IL-6 secretion in primary HOC. To examine the effects of different steroid hormones on IL-6 production, HOC were exposed to estradiol (E2), dihydrotestosterone (DHT), dehydroepiandros terone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We observed that (1) IL-lβ and TNFa induced IL-6 in a dose and time-dependent fashion, (2) TGFβ 1 and 2 enhanced basal and IL-lβ and TNFa induced IL-6 expression, (3) ET-1 elicited a dose-dependent stimulatory effect on IL-6 expression. (4) E2, DHT and DHEA alone and in combination with IL-lβ and TNFa elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basal and IL-lβ and TNFa induced IL-6 expression dose dependently. In conclusion, IL-lβ, TNFα, TGFβ 1 and 2 and ET-1 may participate in the regulation of bone résorption by stimulating IL-6 expression in HOC Dexa inhibits the constitutive and cytokine stimulated IL-6 expression, whereas there is no in vitro evidence that sex steroids exert a major inhibitory effect on the osteoblastic secretion of IL-6 as demonstrated in a primary human bone cell model.

Key words

IL-6 - osteoblasts - cytokines - steroids - regulation