Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte/macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates a wide range of myeloid hematopoietic cells; RNAs coding for many oncogenes and cytokines including GM-CSF have a very short half-life. The motif of AUUUA is a highly conserved sequence in the 3'untranslated regions (3'UTR) of these transcripts and is repeated a number of times in these short-lived cytokines and oncogenes. These sequences play a major role in controlling stability of these transcripts. Human cancer cells were transfected with a chimeric rabbit beta-globin gene linked to either a 58 bp sequence of the AT-rich region from GM-CSF or a control sequence. We have found that irradiation stimulates accumulation of GM-CSF, interleukin-6 (IL-6), and IL-1 beta RNAs. In addition, this accumulation of GM-CSF was at least, in part, a result of increased stabilization of GM-CSF transcripts. Further experiments showed that irradiation increased levels of the chimeric beta-globin transcripts containing AUUUA sequences from GM-CSF, but not those containing the control sequences. Our results suggest that irradiation increases expression of GM-CSF RNA and that posttranscriptional stabilization requiring AUUUA sequences probably is in part one of the mechanisms producing the increased levels of GM-CSF RNA by irradiation.
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PMID:Irradiation increases levels of GM-CSF through RNA stabilization which requires an AU-rich region in cancer cells. 147 71

The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells. While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined. It has been suggested that the effect of IL-1 might be post-transcriptional, exerted through the 5'-untranslated region (5'-UTR). To evaluate the role of IL-1 in CRP gene expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone had no effect on CRP mRNA levels, but when added to IL-6, synergistically enhanced both CRP mRNA levels and transcription, as determined by Northern-blot analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta + IL-6] each induced increases in mRNA levels roughly comparable with observed increases in transcription. These findings indicate that the effect of IL-1 beta on CRP expression is exerted largely at the transcriptional level in this system. This conclusion was confirmed by studies in Hep3B cells transiently transfected with CRP-CAT constructs, each containing 157 bp of the CRP 5'-flanking region but differing in the length of the 5'-UTR from 104 bp to 3 bp. All constructs responded in the same way; IL-6, but not IL-1 beta, induced significant chloramphenicol acetyltransferase (CAT) expression which was synergistically enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta stimulates transcriptional events in the presence of IL-6 and that the upstream 157 bases of the CRP promoter contain elements capable of both IL-6 induction and the synergistic effect of IL-1 beta on transcription.
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PMID:The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level. 764 36

The transcription rates of the rat serine protease inhibitor 2.3 and 2.1 genes (spi 2.3 and spi 2.1), which are normally very low and high, respectively, are inversely modulated during inflammation. Two growth-hormone-response elements (GHRE-I and GHRE-II) maintain the spi 2.1 gene under the stringent control of growth hormone [Le Cam, A., Pantescu, V., Paquereau, L., Legraverend, C., Fauconnier, G. & Asins, G. (1994) J. Biol. Chem. 269, 21532-21539], whereas spi 2.3 appears to escape control by this hormone, despite the presence in its promoter of a functional GHRE-I. A major difference between these two otherwise very similar genes is the presence in spi 2.3 of a specific 348-bp extension of the 3' untranslated region (3' UTR). Inserting this 3' UTR element downstream of the polyadenylation signal or upstream of the spi 2.3 promoter in constructs containing the chloramphenicol acetyltransferase gene strongly decreases basal transcription and inhibits growth-hormone-stimulated transcription, but poorly affects transcriptional stimulation by dexamethasone or interleukin-6. The spi 2.3 3' UTR extension also inhibits, basal and growth-hormone-induced transcription from the spi 2.1 promoter. Repressor activity appears to be distributed throughout the specific extension of the 3' UTR and seems to involve interactions with two types of 5' cis-acting promoter elements. The first is the GAGA box, a key control spi promoter element, whose mutation faithfully reproduces the effects of the 3' UTR silencer on spi 2.1 and spi 2.3 promoters. The second is represented by CCAAT enhancer-binding-protein-(C/EBP)-binding sites, whose functions are severely impaired by the spi 2.3-specific 3' UTR extension. The presence of this silencer in the spi 2.3 gene very likely accounts for the lack of basal of transcription in vivo and for induction of the gene during acute inflammation.
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PMID:Transcriptional repression, a novel function for 3' untranslated regions. 764 61

Angiogenesis, the formation of new blood vessels, is induced by various growth factors and cytokines that act either directly or indirectly. Vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and therefore has a central role in physiological events of angiogenesis. Interleukin-6 (IL-6) expression on the other hand is elevated in tissues that undergo active angiogenesis but does not induce proliferation of endothelial cells. We demonstrate using Northern analysis that treatment of various cell lines with IL-6 for 6-48 h results in a significant induction of VEGF mRNA. The level of induction is comparable to the documented induction of VEGF mRNA by hypoxia or cobalt chloride, an activator of hypoxia-induced genes. In addition, it is demonstrated by transient transfection assays that the effect of IL-6 is mediated not only by DNA elements at the promoter region but also through specific motif(s) located in the 5'-untranslated region (5'-UTR) of VEGF mRNA. Our results imply that IL-6 may induce angiogenesis indirectly by inducing VEGF expression. It is also shown that the 5'-UTR is important for the expression of VEGF. The 5'-UTR of VEGF is exceptionally long (1038 base pairs) and very rich in G + C. This suggests that secondary structures in the 5'-UTR might be essential for VEGF expression through transcriptional and post-transcriptional control mechanisms.
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PMID:Interleukin 6 induces the expression of vascular endothelial growth factor. 855 80

The cDNA insert of the plasmid p14-6 is found to be the 3'-untranslated region (3'-UTR) of the transcription factor for human interleukin-6, NF-IL6. This 3'-UTR is actively transcribed in the revertant cell line RR, which contains the p14-6 plasmid integrated into its genomic DNA. Simultaneously a protein specifically bound to this 3'-UTR is expressed in significantly larger amounts. Its overexpression is apparently related to the reversion of the malignant cellular phenotype. The properties of this protein, named BNF, and possible reasons for its overexpression are discussed, and hypothesis on the mechanism of reversion of the RR cells is proposed.
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PMID:Overexpression of a reversion-related protein in the revertant RR cells. 876 Apr 58

H19 is an imprinted gene developmentally regulated in man and mouse and implicated in various neoplasms. No corresponding protein product has yet been detected, although several open reading frames (ORFs) could be identified along its RNA. The largest ORF found in the human gene could encode a putative 26 kDa protein. We have isolated two H19 cDNAs (AP and ES) that contain this ORF4 and correspond to incomplete copies of the unique 2.3 kb H19 RNA. In transient expression assays, AP was able to synthesize a 26 kDa protein whereas ES was not. With respect to ORF4, ES exhibits a 536 bp long GC-rich 5' untranslated region, whereas AP contains the last 22 nucleotides of this 5'UTR. Using deletions and point mutations, we have found that the length and probably the secondary structure of the 5'UTR strongly hampers the translatability of the RNA. In addition, a potential role of upstream ORFs (uORFs) was detected as stressed by the enhances translation of a construct mutated in uORF3 overlapping ORF4. Interactions between H19 and proteins are indicated by a specific binding between 5'UTR derived RNA segments and two nuclear proteins of about 27 kDa. Our results favor a potential role of these particular structures and binding properties in general trans-regulation of RNA post-transcriptional processes rather than in normal control of H19 mRNA translation.
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PMID:The 5' part of the human H19 RNA contains cis-acting elements hampering its translatability. 899 20

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. Bone mineral density is a complex trait that, presumably, is influenced by multiple genes. Interleukin-6 (IL-6) is an attractive candidate gene for osteoporosis susceptibility, because it has effects on bone cells and has been implicated in the pathogenesis of osteoporosis. Furthermore, previous investigators have identified an association between a 3' UTR polymorphism of the IL-6 gene and BMD. In this study, we searched for linkage and association between this IL-6 gene polymorphism and peak BMD in a large population (812 individuals) of healthy premenopausal sibpairs. Although previous investigators identified only 6 IL-6 alleles, we identified 17 alleles by modifying electrophoretic conditions and evaluating a very large population. We found no evidence for either linkage or association between the IL-6 gene locus and BMD of the spine or hip in either Caucasians or African Americans.
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PMID:Sib pair linkage and association studies between bone mineral density and the interleukin-6 gene locus. 1086 25

The 3'UTR of eukaryotic mRNA is an important regulation region, on which many trans factors act. In recent years, a series of 3'UTRs were shown to have tumor suppressor function, including the 3'UTR of the human nuclear factor for interleukin-6 (NF-IL6 3'UTR). To understand molecular basis for this function, we have tried to isolate genes encoding protein factors acting on the RNA of NF-IL6 3'UTR. Here we show that, by using a yeast three-hybrid system, a cDNA fragment was successfully isolated. This cDNA was allowed to express in E. coli, and its expression product, a polypeptide of ca. 70 amino acids long, was shown to specifically bind to the NF-IL6 3'UTR RNA. A search in GenBank did not reveal homologous sequences. Therefore, this cDNA fragment may be a part of the gene of a novel NF-IL6 3'UTR specific binding protein.
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PMID:Three-hybrid strategy reveals a peptide segment that specifically binds to the 3'-untranslated region of NF-IL6 mRNA. 1100 90

Interactions between the RNA transcript of the tumor suppressor cDNA clone, p14-6 (the 3'untranslated region of the nuclear factor for human interleukin-6; NF-IL6 3'UTR), and the reversion-related proteins BNF, were investigated. It was found that: (1) the recognition site of the RNA for BNFs was a 24-nucleotide segment located within the 3'-proximal U-rich sequence; (2) the BNFs were a group of proteins which may interact with each other before interacting with a site on the RNA as a protein complex; (3) possibly only one protein in the complex, namelyR62, directly bound to the RNA site.
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PMID:On the Molecular Mechanism of the Tumor Suppressor Function of cDNA Clone p14-6. 1223 75

Studies have indicated that inflammation, in conjunction with the production of reactive oxygen species, may play a key role in lung cancer development. In this study, 250 lung cancer patients and 214 controls were genotyped for polymorphisms of the inflammation-related genes prostaglandin synthase-2/cyclooxygenase-2 (COX2/PTGS2), interleukin-6 (IL6), interleukin-8 (IL8) and peroxisome proliferator-activated receptor gamma (PPARg). We found that carriers of the C allele of a polymorphism in the 3'-UTR of COX2 had a significantly increased risk of lung cancer, with odds ratios of 4.28 (95% CI, 2.44-7.49) for homozygotes and 2.12 (95% CI, 1.25-3.59) for heterozygotes. Additionally, we found that an IL8 promoter polymorphism had a protective effect for lung cancer in female subjects, whereas an IL6 promoter polymorphism was only associated with risk of squamous cell carcinoma. This is the first study implicating polymorphisms in inflammatory genes in the risk of lung cancer.
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PMID:Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. 1460 94


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