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

T4-binding globulin (TBG) shares a high degree of homology with two serpin antiproteases, alpha 1-antichymotrypsin (ACT) and alpha 1-antitrypsin (AT), whose synthesis is increased during the acute phase phenomenon, which accompanies trauma, infections, and neoplasms. Interleukin-6 (IL-6) is believed to be the main effector of the acute phase response. When evaluated in human hepatoblastoma-derived (Hep G2) cells exposed to different doses of the recombinant human cytokine for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the secretion of [35S]methionine-labeled TBG, transthyretin (TTR), and albumin. The secretion of ACT and AT was increased. These changes were not due to alterations in the secretory process, since the kinetics of secretion of newly synthesized proteins were not modified. IL-6 did, however, cause a decrease in the steady state levels of mRNA for TTR, TBG, and albumin and an increase in ACT and AT mRNAs. In addition, nuclear run-off assay demonstrated a decrease in the transcription of TTR, TBG, and albumin genes and an increased transcription of the ACT gene. Quantitation of the results showed that changes in the secretion of proteins, in steady state mRNA levels, and in gene transcription were superimposable for each protein, indicating that IL-6 exerts its effect on thyroid hormone-binding proteins mostly at the transcriptional level and that TTR is the thyroid hormone-binding protein showing the most pronounced negative regulation by IL-6. The opposite effect of IL-6 on TBG and the antiproteases, despite their structural homology, underscores gene divergence among these proteins.
Mol Endocrinol 1992 Jun
PMID:Effects of interleukin-6 on the expression of thyroid hormone-binding protein genes in cultured human hepatoblastoma-derived (Hep G2) cells. 132 58

The proto-oncoprotein c-Rel is a member of the nuclear factor kappa B transcription factor family, which includes the p50 and p65 subunits of nuclear factor kappa B. We show here that c-Rel binds to kappa B sites as homodimers as well as heterodimers with p50. These homodimers and heterodimers show distinct DNA-binding specificities and affinities for various kappa B motifs. In particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and beta interferon kappa B sites. In spite of its association with p50 in vitro, however, we found a lymphoid cell-specific nuclear factor in vivo that contains c-Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II, appears to contain the c-Rel homodimer and preferentially recognizes several IL-6 kappa B-related kappa B motifs. Although it has been previously shown that the IL-6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive element in nonlymphoid cells, its activity was found to be repressed in lymphoid cells such as a Jurkat T-cell line. We also present evidence that IL-6 kappa B binding factor II functions as a repressor specific for IL-6 kappa B-related kappa B motifs in lymphoid cells.
Mol Cell Biol 1992 Apr
PMID:A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells. 137 88

The biosynthesis of alternative regulatory complement protein factor H was investigated using both an in vivo rat model and an in vitro rat hepatocyte culture system, and compared to that of C3 component. Subcutaneous injection of a single dose of 20 micrograms of recombinant murine tumor necrosis factor-alpha (rmTNF-alpha) had no effect on factor H liver mRNA levels, while it increased C3 mRNA levels. In correlation with this, serum factor H levels remained unchanged after rmTNF-alpha injection, whereas C3 levels were increased. In contrast in vitro studies showed that rmTNF-alpha had no effect on factor H and C3 expression by rat hepatocytes. Recombinant human interleukin-1 alpha (rhIL-1 alpha) did not alter the expression of factor H, whereas it increased C3 expression, and recombinant human interleukin-6 (rhIL-6) stimulated expression of both proteins. This study shows that TNF-alpha is not directly responsible for the increased levels of factor H observed in vivo during induced inflammation in the rat. Its in vivo effect on C3 secretion might be secondary to the TNF-alpha-induced release of IL-1 and/or IL-6.
Mol Immunol
PMID:Differential modulation of complement factor H and C3 expression by TNF-alpha in the rat. In vitro and in vivo studies. 138 44

Signal transduction in eukaryotic cells is a complex process mediated, normally, by the interaction of soluble extrinsic protein factors and their cognate receptors. One example of this phenomena is the inflammatory cytokine interleukin-6 and the IL-6 receptor. However, the IL-6 receptor, once its ligand is bound, associates with another membrane glycoprotein, gp130, to potentiate the cytokine response. To further understand the basis of this interaction, and its possible implications in cellular transforming events, the corresponding gene(s) must be studied. Here we find that the human gp130 gene product is homologous to two distinct chromosomal loci on chromosomes 5 and 17. Furthermore, the presence of two distinct gp130 gene sequences is restricted to primates and is not found in other vertebrates.
Somat Cell Mol Genet 1992 Sep
PMID:Chromosomal localization of the IL-6 receptor signal transducing subunit, gp130 (IL6ST). 147 13

A porcine interleukin-6 (pIL-6) cDNA has been cloned from pig spleen cDNA library to provide information that would allow us to study IL-6 mRNA expression during pregnancy of several domestic Artiodactyla. The cDNA is 1058 bp long and with a single open reading frame that encodes a 212 amino acid polypeptide with 28-residue signal sequence. It shares 61% and 43% amino acid sequence identity with human and mouse IL-6, respectively. PCR procedures with primers designed from regions of sequence conserved between human and pig have been used to identify IL-6 cDNA in lambda gt11 libraries constructed from day 15-16 (sheep), day 17 (cattle), and day 13-17 (pig) conceptus mRNA. The presence of IL-6 mRNA in elongating preimplantation ovine (days 13-25), porcine (days 13-21), and bovine (days 16-20) conceptuses was also demonstrated by PCR after reverse transcription of total ribonucleic acid with reverse transcriptase and by solution hybridization with a pIL-6 cRNA probe. These observations suggest that IL-6 is a product of these early conceptuses and may be involved in early maternal responses to the presence of an embryo within the uterus.
Mol Reprod Dev 1992 Aug
PMID:Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses. 149 80

3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumour necrosis factor-alpha (TNF) attenuates this process. Inhibition of differentiation by this cytokine, thought to be mediated at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and three diversely regulated genes during the first 24 h of the differentiation process. Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA, which returned to near basal levels within 4-6 h, was observed. In contrast, c-jun mRNA, although rapidly expressed at the induction of differentiation, remained at relatively constant levels throughout the time-course. Exposure of the cells to 5 nM TNF potentiated the accumulation of all three mRNAs but most significantly that of c-jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fos-B were expressed transiently from 30 min to 2 h, while fra-1 mRNA accumulated over an extended period of 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control the expression of genes involved in the terminally differentiated state, was attenuated after exposure of the cells to TNF. Interleukin-6 (IL-6) mRNA was expressed briefly (30 min to 2 h) and again transiently (at 8 h after induction of differentiation). TNF treatment markedly enhanced accumulation of IL-6 message. We propose that an increased cellular content of one or more transcription factors or the suppression of C/EBP may be responsible for the attenuation of differentiation induced by exposure of the cells to TNF.
J Mol Endocrinol 1992 Aug
PMID:Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by tumour necrosis factor-alpha. 151 26

Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages. 152 Apr 90

In chicken myeloid cells but not in erythroid cells, kinase-type oncogenes activate expression of the chicken myelomonocytic growth factor (cMGF). The autocrine loop established this way plays a key role in lineage-specific cooperation of nuclear and kinase-type oncogenes in retrovirally induced myeloid leukemia. In this report, we describe the cloning of the cMGF gene, including its promoter. The structure of the cMGF gene is homologous to those of the granulocyte colony-stimulating factor and interleukin-6 genes. Expression from reporter constructs containing the cMGF promoter is specific to myelomonocytic cells. Kinases activate cMGF at the transcriptional level in macrophages and strongly induce reporter expression in myelomonocytic cells.
Mol Cell Biol 1992 Apr
PMID:Structure of the chicken myelomonocytic growth factor gene and specific activation of its promoter in avian myelomonocytic cells by protein kinases. 154 24

Interleukin-6 (IL-6) relays an important signal to hepatocytes during the early stages of an acute inflammatory response, causing an alteration in the expression of several major defense proteins. Additional regulation of this signal could occur either by altering the number of IL-6 receptors (IL-6-R) or of the signal transducing protein, gp130. We employed ribonuclease protection assays to measure the expression of IL-6-R and gp130 mRNA in primary rat hepatocytes in response to IL-6, interleukin-1, dexamethasone, and combinations thereof. Dexamethasone increases receptor mRNA levels 2.7-fold above controls but has no detectable effect on that of gp130. Such treatment increased surface expression of IL-6-R from 600 receptors per cell to greater than 6000, without a change in Kd (2.5-4.6 x 10(-10) M). In contrast to the stimulatory effect of the steroid signal, the inflammatory cytokines, individually and together, down-modulated both the mRNA and the cell surface expression of IL-6-R. These findings demonstrate for the first time that a sensitive control system exists between inflammatory mediators and IL-6-R.
Mol Biol Cell 1992 Jan
PMID:Differential regulation of interleukin-6 receptor and gp130 gene expression in rat hepatocytes. 155 Sep 52

The c-myb proto-oncogene is abundantly expressed in tissues of hematopoietic origin, and changes in endogenous c-myb genes have been implicated in both human and murine hematopoietic tumors. c-myb encodes a DNA-binding protein capable of trans-activating the c-myc promoter. Suppression of both of these proto-oncogenes was shown to occur upon induction of terminal differentiation but not upon induction of growth inhibition in myeloid leukemia cells. Myeloblastic leukemia M1 cells that can be induced for terminal differentiation with the physiological hematopoietic inducers interleukin-6 and leukemia inhibitory factor were genetically manipulated to constitutively express a c-myb transgene. By using immediate-early to late genetic and morphological markers, it was shown that continuous expression of c-myb disrupts the genetic program of myeloid differentiation at a very early stage, which precedes the block previously shown to be exerted by deregulated c-myc, thereby indicating that the c-myb block is not mediated via deregulation of c-myc. Enforced c-myb expression also prevents the loss in leukemogenicity of M1 cells normally induced by interleukin-6 or leukemia inhibitory factor. Any changes which have taken place, including induction of myeloid differentiation primary response genes, eventually are reversed. Also, it was shown that suppression of c-myb, essential for terminal differentiation, is not intrinsic to growth inhibition. Taken together, these findings show that c-myb plays a key regulatory role in myeloid differentiation and substantiate the notion that deregulated expression of c-myb can play an important role in leukemogenicity.
Mol Cell Biol 1992 Jun
PMID:Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis. 158 53


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