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  • Title: Interleukin-1 beta induces cyclic AMP formation in isolated human osteoblasts: a signalling mechanism that is not related to enhanced prostaglandin formation.
    Author: Bornefalk E, Ljunghall S, Johansson AG, Nilsson K, Ljunggren O.
    Journal: Bone Miner; 1994 Nov; 27(2):97-107. PubMed ID: 7536063.
    Abstract:
    Interleukin-1 (IL-1) is a potent stimulator of bone resorption. Induction of osteoclastic bone resorption by various endocrine or paracrine factors is mediated via the osteoblasts. We have therefore investigated the effects of IL-1 beta on cell signalling in isolated human osteoblasts. Special interest was focused on prostaglandin synthesis, since indomethacin, an inhibitor of prostaglandin synthesis, partly inhibits IL-1-induced bone resorption. IL-1 beta, at and above 0.3 pM, dose dependently stimulated PGE2 formation in isolated human osteoblasts, with half maximal stimulation, EC50, at 3 pM. Treatment with the calcium ionophore A23187 (1 microM), or with forskolin (30 microM), also stimulated PGE2 formation in human osteoblasts. The time-course for IL-1 beta-induced PGE2 formation was similar to that of forskolin, with a significant increase in the formation of PGE2 seen after 1 h. In contrast, A23187-induced PGE2 formation was seen within minutes. IL-1 beta stimulated the accumulation of cyclic AMP in isolated human osteoblasts incubated for 15 min. This increase in cyclic AMP formation was not secondary to PGE2 formation since it was not blocked by the addition of indomethacin (1 microM). Pretreatment with the phosphodiesterase inhibitor IBMX did not augment IL-1 beta-induced PGE2 formation, nor did the protein kinase A inhibitor Rp-cAMPs inhibit IL-1 beta-induced PGE2 formation, suggesting that cyclic AMP does not mediate the stimulatory effect of IL-1 on PGE2 formation. We conclude that IL-1 beta enhances the formation of cyclic AMP as well as PGE2 in primary cultures of isolated human osteoblasts. The IL-1 beta-induced cyclic AMP formation is, however, not related to the enhanced prostaglandin formation. The findings implicate that both cyclic AMP- and PGE2-formation in osteoblasts might be involved as independent mediators of IL-1 beta-induced bone resorption.
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