Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures.
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)
Tarjan
G
G
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois, USA.
Stern
P H
PH
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*
D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D014284:Triiodothyronine