PMID- 9792466 OWN - NLM STAT- MEDLINE DCOM- 19990108 LR - 20061115 IS - 0947-7349 (Print) IS - 0947-7349 (Linking) VI - 106 IP - 4 DP - 1998 TI - Regulation of interleukin-6 expression in human osteoblastic cells in vitro. PG - 324-33 AB - 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-1beta (IL-1beta), Tumor Necrosis Factor alpha (TNFalpha), Transforming Growth Factor beta1 and 2 (TGFbeta 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), dehydroepiandrosterone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We observed that (1) IL-1beta and TNFalpha induced IL-6 in a dose and time-dependent fashion, (2) TGFbeta 1 and 2 enhanced basal and IL-1beta and TNFalpha 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-1beta and TNFalpha elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basal and IL-1beta and TNFalpha induced IL-6 expression dose dependently. In conclusion, IL-1beta, TNFalpha, TGFbeta 1 and 2 and ET-1 may participate in the regulation of bone resorption 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. FAU - Hierl, T AU - Hierl T AD - Ruprecht-Karls-University of Heidelberg, Department of Medicine, Germany. FAU - Borcsok, I AU - Borcsok I FAU - Sommer, U AU - Sommer U FAU - Ziegler, R AU - Ziegler R FAU - Kasperk, C AU - Kasperk C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 0 (Cytokines) RN - 0 (Endothelins) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Lymphotoxin-alpha) RN - 0 (RNA, Messenger) RN - 0 (Steroids) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Aged MH - Aged, 80 and over MH - Blotting, Northern MH - Cells, Cultured MH - Cytokines/pharmacology MH - Endothelins/pharmacology MH - Female MH - Humans MH - Interleukin-1/pharmacology MH - Interleukin-6/*biosynthesis MH - Lymphotoxin-alpha/pharmacology MH - Male MH - Middle Aged MH - Osteoblasts/drug effects/*metabolism MH - RNA, Messenger/biosynthesis/isolation & purification MH - Steroids/pharmacology MH - Stimulation, Chemical MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1998/10/29 00:00 MHDA- 1998/10/29 00:01 CRDT- 1998/10/29 00:00 PHST- 1998/10/29 00:00 [pubmed] PHST- 1998/10/29 00:01 [medline] PHST- 1998/10/29 00:00 [entrez] AID - 10.1055/s-0029-1211993 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 1998;106(4):324-33. doi: 10.1055/s-0029-1211993.