Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production
| Autor: | P Seckinger, J Klein-Nulend, C Alander, R C Thompson, J M Dayer, L G Raisz |
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| Rok vydání: | 1990 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 145:4181-4184 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.145.12.4181 |
| Popis: | Inhibitory factors towards IL-1 have been identified in the urine and in the supernatants of human monocyte cultures and have been shown to act as receptor antagonists. We have investigated whether a natural inhibitor purified from human urine (uIL-1ra) and a recombinant molecule expressed using the gene for an IL-1 antagonist isolated from monocytes (rIL-1ra) can alter responses to human rIL-1 alpha in organ cultures of fetal rat long bones and neonatal mouse calvariae. The two preparations probably contained similar or identical molecules, because an antibody to rIL-1ra reacted with uIL-1ra by Western blot analysis. uIL-1ra and rIL-1ra specifically blocked stimulation of bone resorption by rIL-1 in both culture systems, as well as the increase in PGE2 production in cultured calvariae. Resorptive effects of parathyroid hormone and TNF-alpha were not blocked. The uIL-1ra preparation had some intrinsic resorbing activity, but on gel chromatography this appeared in fractions that eluted earlier than uIL-1ra. Concentration ratios of rIL-1ra to rIL-1 as low as 10 could block the resorptive response of fetal rat long bones, whereas concentration ratios of 100 to 1000 were required to block IL-1 action on neonatal mouse calvariae. The inhibitory effects appeared to be competitive, because increasing concentrations of IL-1 overcame the block of bone resorption in both systems and the inhibition of PGE2 production in calvariae. |
| Databáze: | OpenAIRE |
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