Interleukin-11 mRNA stabilization in phorbol ester-stimulated primate bone marrow stromal cells.
AUTOR(ES)
Yang, L
RESUMO
12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulation of PU-34 cells, a primate bone marrow stromal cell line, resulted in a prolonged elevation of interleukin-11 (IL-11) mRNA, which can be inhibited by protein synthesis inhibitors. Nuclear run-on assays and actinomycin D experiments demonstrated that the up-regulation of IL-11 gene expression is mainly controlled at the posttranscriptional level through the protein kinase C (PKC) pathway. Inhibition of PKC activity by calphostin C generated an IL-11 mRNA degradation intermediate in TPA-stimulated PU-34 cells. This intermediate retains the 5' untranslated region (5'UTR) and coding region of the IL-11 mRNA but has lost the poly(A) tail and the 3'UTR. The mechanisms underlying IL-11 mRNA stabilization were further investigated by transfections with a variety of chimeric IL-11 constructs and deletion mutants. Two important observations were made from these transient expression experiments: (i) the same 3'UTR of IL-11 mRNA shown to confer instability in one chimeric transcript may not function as a destabilizer in another chimeric RNA, and (ii) the 5'UTR, coding region, and 3'UTR all contribute to IL-11 mRNA decay, and labile IL-11 deletion transcripts are not necessarily stabilized by TPA stimulation. Our study suggests that multiple regions within the IL-11 mRNA are involved in TPA-stimulated IL-11 mRNA stabilization, possibly through a unique RNA folding conformation involving interactions of various RNA sequences within the IL-11 mRNA molecule.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=231324Documentos Relacionados
- Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.
- Overexpression of protein kinase C beta 1 enhances phospholipase D activity and diacylglycerol formation in phorbol ester-stimulated rat fibroblasts.
- Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells.
- Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer.
- Recombinant tumor necrosis factor alpha and interleukin 1 alpha increase expression of c-abl protooncogene mRNA in cultured human marrow stromal cells.