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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of interleukin-6 (IL-6) gene in human HepG2 and HeLa cells was induced by treatment with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), phorbol 12-myristate 13-acetate, or dibutyryl cyclic AMP. These agents enhanced the expression of chloramphenicol acetyltransferase (CAT) activity in cells transfected with chimeric CAT genes driven by the transcriptional regulatory regions of human IL-6 gene. Both induced and basal levels of CAT expression were severely repressed upon co-transfection of expression vectors encoding the adenoviral E1A289R or E1A243R protein. The conserved region 1 of E1A proteins was required for this activity. IL-6-CAT expression could also be induced by co-transfecting expression vectors containing cDNAs of the catalytic subunit of protein kinase A or c-jun. E1A repressed transcriptional induction by these agents as well. Similar inhibition was observed when a CAT gene driven by the NF kappa B element of the IL-6 gene was used as a reporter plasmid. In a cell line stably transfected with the E1A gene, IL-1 or TNF-alpha failed to induce IL-6 mRNA. Electrophoretic mobility shift assays were carried out with nuclear extracts of these cells using, as probes, the NF kappa B element or the multiple regulatory element of the IL-6 gene. With either probe, additional faster migrating DNA-protein complexes were formed in the extracts of E1A-expressing cells as compared with the extracts of the corresponding control cells. Experiments with NF kappa B antibody revealed differences between the different DNA-protein complexes formed in the extract of E1A-expressing cells. These observations suggest that E1A represses IL-6 gene transcription by interfering with the formation of appropriate DNA-protein complexes.
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PMID:Transcriptional repression of interleukin-6 gene by adenoviral E1A proteins. 133 71

NF-IL6 and NF-kappa B are nuclear proteins supposed to play an important role in the regulation of acute-phase protein synthesis and inflammatory response against infection and tissue injury as a host defence mechanism. In addition the promoter region of the interleukin-6 (IL-6) gene has a NF-kappa B binding motif as well as a NF-IL6 binding site. Considering of these facts, we come to investigate that there may be a synergistic effect between NF-IL6 and NF-kappa B in the regulation of IL-6 gene expression. In order to study it, some combinations of expression vectors NF-IL6 cDNA, NF-kappa B (p50/p65) cDNA and reporter plasmid K18-CAT which contains human IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) gene, were transfected into Jurkat cells and the CAT activities were examined. Co-transfection of NF-IL6 and NF-kappa B (p50/p65) cDNA revealed a dramatic increase of acetylated [14C] chloramphenicol, and its CAT activity reached to 40%. Then, co-transfection of NF-IL6 and NF-kappa B subunit p65 alone showed a high level of CAT activity, too. When 5' deletion mutant reporter plasmid K9-CAT lacking the NF-IL6 binding site was used, co-transfection of NF-IL6 and NF-kappa B (p50/p65) showed low level of CAT activity. These results indicate that there is a synergistic effect between NF-IL6 and NF-kappa B (p50/p65) in IL-6 gene regulation. Among two subunits of NF-kappa B (p50/p65), p65 seems to play an important role rather than p50 does in synergism between NF-IL6 and NF-kappa B. Besides, this synergistic function comes to work only when NF-IL6 binds to its binding site of IL-6 promoter region.
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PMID:[Synergism between transcription factors NF-IL6 and NF-kappa B in IL-6 gene regulation]. 142

The rat hemopexin (Hx) gene was isolated and studies of its transcriptional regulation initiated. For analysis by a transient expression assay, the sequence between -2400 and +21 and sequential 5' truncates were linked to the chloramphenicol acetyltransferase (CAT) gene. HepG2 cells transfected with these CAT constructs were treated with conditioned medium of lipopolysaccharide stimulated human monocytes, interleukin-1 (IL-1) or interleukin-6 (IL-6). The activities of putative regulatory regions joined to the SV40 promoter indicated that the flanking region of the rat Hx gene from -209 to -104 contains three functional regions designated proximal regulatory regions; PRR-I (-209 to -173), -II (-178 to -158) and -III (-154 to -104). We found that PRR-II contains a different class of IL-6 responsive element (RE) from that reported for the human Hx gene, and that PRR-I and PRR-III participate in the basal expression of rat Hx in HepG2 cells.
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PMID:Identification of an interleukin-6 responsive element and characterization of the proximal promoter region of the rat hemopexin gene. 159 80

Interleukin-6 is a pleiotropic cytokine that has a major role in the coordination of the hepatic acute phase response. In order to more fully understand this role, we have examined the interleukin-6 induction of T kininogen, a cysteine protease inhibitor and a major acute phase reactant in the rat. Using deletional analysis and site-directed mutagenesis of T kininogen-chloramphenicol acetyltransferase fusion constructs transfected into HepG2 hepatoma cells, we have identified two similar interleukin-6 response elements within 250 base pairs of the transcription start site. These two response elements are functionally interdependent. The sequences of these two elements match the consensus sequence for the previously described Type B interleukin-6 response element. Interleukin-6 signal transduction via two Type B elements has not been observed previously in vivo. A DNA fragment encompassing these response elements forms the same protein complex with nuclear extracts from both untreated and interleukin-6-treated cells.
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PMID:Identification of sequences mediating interleukin-6 induction of a rat T kininogen gene. 165 51

Rat T-kininogen (T-KG), a cysteine protease inhibitor, is an acute phase reactant which is induced to high levels in response to inflammation. Both hormones and cytokines participate in this regulation. To investigate the cis-acting elements responsible for the induction of gene expression, various 5'-fragments of the rat T-KG gene were fused to a chloramphenicol acetyltransferase marker gene. These constructs were transfected into a rat hepatoma cell line which was then treated with tumor necrosis factor or interleukin-6 or both cytokines. Expression of the chloramphenicol acetyltransferase gene was induced with interleukin-6 treatment, but suppressed by tumor necrosis factor. The 5'-region of the T-KG gene responsible for conferring both of these effects was localized between nucleotides -404 to -210 upstream of the transcription start site. Fragments containing this region were found to be effective in either orientation, and could also regulate a heterologous promoter.
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PMID:Differential regulation of rat T-kininogen by tumor necrosis factor and interleukin-6. 170

Previously we described a cell line OCI-LY3 derived from a patient with non-Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter.
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PMID:Regulation of interleukin-6 expression in the lymphoma cell line OCI-LY3. 191 71

Deregulated c-fos expression in the rat pheochromocytoma cell line, PC-12, causes pronounced downregulation of nerve growth factor (NGF)-induced c-fos and c-jun activation, accompanied by a block in NGF-induced differentiation of PC-12 cells. The FOS-expressing PC-12 cells were exposed to diverse agents such as NGF, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), dibutyryl cyclic adenosine 3',5' monophosphate (db cAMP), and Ca-ionophore; and the expression of egr-1, c-fos, c-jun, jun-B, and jun-D was analyzed. Pronounced downregulation of c-fos, c-jun, and--to a lesser extent--jun-B was observed on treatment with NGF, bFGF, db cAMP, and Ca-ionophore, whereas EGF-induced activation of these early response genes was not inhibited in FOS-expressing PC-12 cells. Ca-ionophore- and db cAMP-induced egr-1 activation in PC-12 fos cells was completely inhibited. Both parent and PC-12 fos cells expressed similar high basal levels of jun-D, whose expression was the least regulatable by all of these agents. Transfection of fos promoter-chloramphenicol acetyltransferase (promoter-CAT) plasmid into these stable FOS-expressing PC-12 cells revealed that these effects are exerted at the fos promoter level.
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PMID:Transcriptional regulation of early growth response genes in FOS-expressing PC-12 cells. 196 43

The serum concentration of rat T1 kininogen increases 20-30-fold in response to acute inflammation, an induced hepatic synthesis regulated primarily at the transcriptional level. To analyze the cis-regulatory elements responsible for the induced transcription, we fused a 1.6-kilobase segment of the rat T1 kininogen promoter to a reporter gene, chloramphenicol acetyltransferase (CAT). The resultant chimeric DNA was transfected into cultured cells. In transient transfection assays, this 5'-flanking sequence was sufficient to confer cell-specific expression: CAT activity was readily detectable when the construct was transfected into liver-derived cells, but it was not detectable in nonliver cells. Furthermore, when liver cells (Hep3B) transfected with this construct were treated with conditioned medium prepared from activated mixed lymphocyte cultures or with recombinant interleukin-6 (IL-6), a 5-fold increase in CAT activity was detected. Addition of dexamethasone to the conditioned medium or to IL-6 showed synergistic effects and resulted in a 10-fold increase in CAT activity. In contrast, when IL-1 was used with IL-6, induction of CAT activity was inhibited. Deletion analyses revealed two regions important for tissue-specific and induced regulation of T1 kininogen: sequences proximal to base pair -73 conferred enhanced expression in liver-derived cells and a distal region that conferred responsiveness to conditioned medium, recombinant IL-6, and dexamethasone. This responsive element had properties of an inducible transcriptional enhancer, and it was functional in both liver and nonliver cells when placed immediately upstream of a thymidine kinase promoter.
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PMID:Interleukin-6 responsiveness and cell-specific expression of the rat kininogen gene. 199 68

Human C-reactive protein (CRP) is the major acute phase reactant during inflammation. Regulation of CRP gene expression has been studied in two experimental systems: transgenic mice and human hepatoma cells. In the first system the human CRP gene flanked by approximately 10(4) bases of 5' and 3' sequences is expressed in a liver-specific and inducible manner. The chromatin configuration of the CRP transgene is characterized by the presence of constitutive and inducible liver-specific DNase I-hypersensitive sites. Inducible sites map precisely at the level of the CRP promoter region. In hepatoma cells we analysed the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene driven by various segments of the CRP promoter. This latter approach has led to the identification of promoter elements responsive to interleukin-6 and of hepatocyte-specific nuclear proteins that interact with them.
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PMID:Regulation of the human C-reactive protein gene, a major marker of inflammation and cancer. 217 Aug 8

The promoter region of the interleukin-6 (IL-6) gene has a putative NF-kappa B-binding site. We found that a fragment of the IL-6 promoter containing the site specifically binds highly purified NF-kappa B protein and the NF-kappa B protein in nuclear extracts of phorbol ester-induced Jurkat cells. Mutations of the NF-kappa B site abolished complex formation with both purified NF-kappa B and the nuclear extract protein. Transient expression of chloramphenicol acetyltransferase (CAT) plasmids containing the IL-6 promoter revealed very little activity of the promoter in U-937 monocytic cells and in HeLa cells before stimulation. However, stimulation of U-937 and HeLa cells by inducers of NF-kappa B led to a dramatic increase in CAT activity. Mutations in the NF-kappa B-binding site abolished inducibility of IL-6 promoter-cat constructs in U-937 cells by lipopolysaccharide, tumor necrosis factor alpha, the double-stranded RNA poly(IC), or phytohemagglutinin and in HeLa cells by tumor necrosis factor alpha and drastically reduced but did not completely eliminate inducibility in HeLa cells stimulated by double-stranded RNA poly(IC) or phorbol 12-myristate 13-acetate. These results suggest that NF-kappa B is an important mediator for activation of the IL-6 gene by a variety of IL-6 inducers in both U-937 and HeLa cells and that alternative inducible enhancer elements contribute in a cell-specific manner to IL-6 gene induction. Because NF-kappa B is involved in the control of a variety of genes activated upon inflammation, NF-kappa B may play a central role in the inflammatory response to infection and tissue injury.
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PMID:Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. 218 31


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