Cortisol modulates the actions of interleukin-1 alpha on bone formation, resorption, and prostaglandin production in cultured mouse parietal bones.
Previous studies have shown that both interleukin-1 (IL-1) and glucocorticoids inhibit collagen synthesis in bone organ and cell cultures. In this study we examined their interactions in cultured neonatal mouse parietal bones. IL-1 alpha stimulated [3H]thymidine incorporation. Cortisol decreased thymidine incorporation, but did not block the effect of IL-1. Both cortisol and IL-1 alpha decreased the incorporation of [3H]proline into collagenase-digestible protein (CDP) and reduced alpha 1(I)procollagen mRNA levels at 72 h. Noncollagen protein (NCP) labeling was increased by IL-1 and decreased by cortisol. In the presence of cortisol, IL-1 alpha (6 pM) increased CDP as well as NCP labeling. The increase in CDP labeling was paralleled by an increase in alpha 1(I)procollagen mRNA, suggesting a pretranslational site for the cortisol-IL-1 alpha interaction. In the same bones, cortisol consistently blocked IL-1 alpha-stimulated 45Ca release and prostaglandin E2 (PGE2) production. The ability of IL-1 alpha to increase CDP in the presence of cortisol was the same in the presence or absence of indomethacin, an inhibitor of PGE2 synthesis, or aphidicholin (30 microM), an inhibitor of DNA synthesis, indicating that the reversal was neither PG mediated nor dependent on cell proliferation. In conclusion, our results demonstrate that IL-1 inhibits collagen, but not NCP or DNA, synthesis and that cortisol inhibits IL-1 alpha-induced bone resorption and PGE2 production and reverses its inhibitory effect on collagen synthesis in cultured neonatal mouse calvariae.
University of Connecticut Health Center, Farmington 06032.
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Marusić
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LG
Raisz
D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D003094:Collagen / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D010012:Osteogenesis / Q000187:drug effects*; D010294:Parietal Bone / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism
D007375:Interleukin-1; D011453:Prostaglandins; D003094:Collagen; D013936:Thymidine; D006854:Hydrocortisone; D007213:Indomethacin