Interleukin 6 is autoregulated by transcriptional mechanisms in cultures of rat osteoblastic cells.
AUTOR(ES)
Franchimont, N
RESUMO
Interleukin 6 (IL-6), a cytokine produced by skeletal cells, stimulates osteoclast recruitment. The IL-6 soluble receptor (sIL-6R) increases IL-6 activity, and IL-6 and sIL-6R levels are increased in conditions of increased bone resorption. We examined the production of IL-6 by primary rat osteoblasts (Ob cells) cultured in the presence of IL-6 and sIL-6R. IL-6 alone did not induce IL-6 transcripts, but IL-6 was stimulatory in the presence of sIL-6R. Furthermore, sIL-6R by itself increased IL-6 transcripts. Cycloheximide superinduced IL-6 transcripts and did not prevent the effect of IL-6 and sIL-6R. IL-6 in the presence of sIL-6R stimulated IL-6 rates of transcription and the activity of IL-6 promoter fragments in transiently transfected Ob cells. 5' deletions of the IL-6 promoter and targeted mutations of the multiple response element (MRE)/cAMP responsive element (CRE), the nuclear factor for IL-6 (NF-IL-6), and the nuclear factor-kappaB (NF-kappaB) binding sites indicated that NF-IL-6 and NF-kappaB, in combination with MRE/CRE, binding sites are required for the induction of the IL-6 promoter by IL-6. In conclusion, IL-6 induces its own synthesis in osteoblasts by transcriptional mechanisms. This positive feedback may be important in conditions of increased bone resorption.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=508365Documentos Relacionados
- Interleukin-6 attenuates agonist-mediated calcium mobilization in murine osteoblastic cells.
- Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells.
- Distinct regulation of the interleukin-1 and interleukin-6 response elements of the rat haptoglobin gene in rat and human hepatoma cells.
- Alpha-actinin synthesis can be modulated by antisense probes and is autoregulated in non-muscle cells.
- Id gene expression and its suppression by 1,25-dihydroxyvitamin D3 in rat osteoblastic osteosarcoma cells.