title: Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures.
abstract: It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3'-triiodothyronine (T3) on bone resorption (45Ca release) and on the IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T3 alone increased 45Ca release significantly only at a fairly high concentration (10(-6)M) under the conditions used. T3 alone, over a 10(-11)-10(-6) M concentration range, failed to elicit a detectable effect on the medium IL-6 content. However, T3 potentiated the stimulatory effect of interleukin-1 beta (IL-1 beta) on IL-6 production in a dose-dependent manner. T3, 10(-8) M, also significantly increased IL-1 beta-stimulated calcium release. Inhibition of IL-1 beta with 1 muM interleukin-1 receptor antagonist (IL-1ra) abrogated the potentiating effects of T3 on IL-1 beta-stimulated IL-6 production and blocked the combined effect of T3 and IL-1 beta on 45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL-1 beta, as well as the combined effect of IL-1 beta and T3 on resorption and IL-6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 microM prostaglandin E1 (PGE1) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1 beta, T3 increased bone resorption at much lower concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois, USA.
authors.forename: G
authors.initials: G
authors.lastname: Tarjan
authors.forename: P H
authors.initials: PH
authors.lastname: Stern
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D003470:Culture Media; D004357:Drug Synergism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology* / Q000502:physiology; D018878:Limb Buds / Q000187:drug effects / Q000196:embryology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D014284:Triiodothyronine