Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-4 and IL-10 inhibit the cytokine production and mRNA expression by monocytes/macrophages. To investigate the molecular mechanism of the inhibitory effect on transcriptional or post-transcriptional regulation of IL-6 gene expression by IL-4 and IL-10, we studied IL-6 production, expression level of IL-6 mRNA, IL-6 promoter activity, transcriptional activity of NF-kappaB and NF-IL-6, and IL-6 mRNA stability in human monocytic cell lines, THP-1 and U937, stimulated by PMA and LPS in the absence or the presence of IL-4 or IL-10. Both IL-4 and IL-10 were seen to inhibit IL-6 production and the expression of IL-6 mRNA in both monocytic cell lines studied. In chloramphenicol acetyltransferase assays, utilizing the transient transfection of a chloramphenicol acetyltransferase reporter plasmid containing the IL-6 gene promoter, IL-4, but not IL-10, suppressed the transcriptional activity of the IL-6 gene promoter stimulated by PMA and LPS. Electrophoretic mobility shift assays showed that IL-4, but not IL-10, inhibited nuclear NF-kappaB activity, and that IL-4 and IL-10 did not affect NF-IL-6 activity. On the other hand, IL-10 enhanced the degradation of IL-6 mRNA in a mRNA stability assay. These results suggest that IL-4 may inhibit the transcription of the IL-6 gene by affecting NF-kappaB binding activity, while IL-10 may inhibit the IL-6 mRNA levels post-transcriptionally, without suppressing promoter activity. Therefore, we conclude that IL-4 and IL-10 inhibit IL-6 production by different mechanisms in human monocytic cell lines.
 ...
PMID:Differential regulation of IL-6 gene transcription and expression by IL-4 and IL-10 in human monocytic cell lines. 878 24

The "long pentraxins" are an emerging family of genes that have conserved in their carboxy-terminal halves a pentraxin domain homologous to the prototypical acute phase protein pentraxins (C-reactive protein and serum amyloid P component) and acquired novel amino-terminal domains. In this report, a genomic fragment of 1371 nucleotides from the human "long pentraxin" gene PTX3 is characterized as a promoter on tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta exposure in transfected 8387 human fibroblasts by chloramphenicol acetyltransferase and RNase protection assays. In the same cells, the PTX3 promoter does not respond to IL-6 stimulation. Furthermore, IL-1beta and TNFalpha responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-kappaB element which is shown to be necessary for induction and able to bind p50 homodimers and p65 heterodimers but not c-Rel. Mutants in this site lose the ability to bind NF-kappaB proteins and to respond to TNFalpha and IL-1beta in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-kappaB site do not seem to play a major role for cytokine responsiveness. Finally, cotransfection experiments with expression vectors validate that the natural promoter contains a functional NF-kappaB site.
 ...
PMID:Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation. 907 34

Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of epithelial origin and in normal tissues during events involving matrix remodeling such as the cycling endometrium. We previously observed that inflamed ductule and acinar epithelia in the prostate also overexpress matrilysin. The presence of infiltrating macrophages in these areas prompted us to determine if factors secreted from monocytes could induce matrilysin expression in a human prostatic cell line. Conditioned media collected from the monocyte cell line THP-1 following lipopolysaccharide treatment substantially induced matrilysin protein and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not by equimolar concentrations of recombinant tumor necrosis factor-alpha or IL-6. The matrilysin-inducing activity of THP-1 conditioned medium was completely abrogated by preincubation with a neutralizing antibody to IL-1beta. Transient transfection analyses with a chimeric human matrilysin promoter-chloramphenicol acetyltransferase reporter construct demonstrated that IL-1beta activates transcription through the matrilysin promoter in LNCaP cells. This is the first report of matrilysin induction by an inflammatory cytokine in a cell line of epithelial origin, and the results suggest a potential mechanism for the overexpression of matrilysin in inflamed ducts and glands of the prostate.
 ...
PMID:Interleukin-1beta secreted from monocytic cells induces the expression of matrilysin in the prostatic cell line LNCaP. 916 49

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.
 ...
PMID:Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53. 938 10

Human cytomegalovirus (HCMV) is a common cause of morbidity and mortality in immunosuppressed patients, especially transplant recipients. In this population, infection is frequently due to reactivation of latent virus. The major immediate early promoter of HCMV controls production of immediate early gene products, which are both trans- and cis-active and are responsible for reactivation. Activation of this promoter is therefore a crucial step in regulation of reactivation infection. It is known that there are cAMP-response elements in the HCMV major immediate early promoter. We hypothesized that prostaglandins (PG), like PGE2, which are known to increase cAMP, as well as cytokines known to be released during acute inflammation, may be important in the regulation of this promoter and thus in reactivation of HCMV. To examine this, we transfected pCAT760, a plasmid containing the major immediate early promoter of HCMV upstream of a chloramphenicol acetyltransferase (CAT) gene, into THP-1 cells. These cells were subsequently stimulated with PGE2 and/or one of a variety of cytokines. We found that PGE2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta each upregulated the HCMV major immediate early promoter. TNF-alpha, IL-1 beta, IL-6, and IL-10 were each synergistic or additive with PGE2 in upregulating the promoter. Since PGE2 and the cytokines are all products of activated macrophages, we suggest that acute inflammation and macrophage activation may predispose to reactivation of latent HCMV.
 ...
PMID:Synergistic activation of the human cytomegalovirus major immediate early promoter by prostaglandin E2 and cytokines. 945 65

Tissue inhibitor of metalloproteinases-1 (TIMP-1) can be regulated by gp130 cytokines such as IL-6 and oncostatin M (OSM). Polymerase chain reaction deletion analysis of the murine TIMP-1 proximal promoter in chloramphenicol acetyltransferase reporter gene constructs identified an AP-1 element (-59/-53) that allows maximal responsiveness to OSM in HepG2 cells. Fos and Jun nuclear factors bound constitutively to this site as identified by supershift analysis in electrophoretic mobility shift assays, and oncostatin M (but not IL-6) induced an additional "complex 2" that contained c-Fos and JunD. OSM stimulated a rapid and transient increase in c-Fos mRNA and nuclear protein that coincided with complex 2 formation. Phorbol 13-myristate 12-acetate could also induce c-Fos but could not regulate the TIMP-1 reporter gene constructs. Transfection studies also showed that 3'-deletion of sequences downstream of the transcriptional start site (+1/+47) markedly reduced OSM -fold induction. Nuclear factors bound to SP1 and Ets sequences were detected, but were not altered upon OSM stimulation. Although OSM and IL-6 induced STAT (signal transducers and activators of transcription) factors to bind a high affinity Sis-inducible element DNA probe, binding to homologous TIMP-1 promoter sequences was not detected. Thus, OSM (but not IL-6) stimulates c-Fos, which participates in maximal activation of TIMP-1 transcription, likely in cooperation with other factors such as SP1 or as yet unidentified mechanisms involving the +1 to +47 region of the promoter.
 ...
PMID:Oncostatin M stimulates c-Fos to bind a transcriptionally responsive AP-1 element within the tissue inhibitor of metalloproteinase-1 promoter. 947 76

We have investigated the effects of IL-1 and IL-6 on human complement factor I (CFI) production by Hep G2 cells. IL-6 treatment caused a dose- and time-dependent increase in CFI secretion while IL-1 did not demonstrate such effects. The increase in CFI synthesis correlated with increase in CFI mRNA levels. The half-life of CFI mRNA in untreated cells was approx. 23 h and this was increased to 31 h (26% increase) following induction with IL-6. The IL-6 induced increase in CFI gene expression was inhibited by actinomycin D indicating regulatory effects at the level of transcription. Nuclear run-on experiments showed that IL-6 increased the rate of CFI gene transcription 4.2-fold. Transient transfection analysis of chloramphenicol acetyltransferase reporter gene constructs containing truncated segments of the 5'-flanking region of CFI gene showed that the cis-acting sequence(s) controlling the IL-6 inducible transcription resides in an 83 bp region located between -738 bp and -655 bp relative to the transcription start site. Our results indicate that the upregulation of CFI gene expression by IL-6 involves a coordinate effort at the level of transcription and mRNA stability, with the enhanced rate of transcription being the principal mechanism.
 ...
PMID:Transcriptional and post-transcriptional regulation of complement factor I (CFI) gene expression in Hep G2 cells by interleukin-6. 980 75

The expression of the interleukin (IL-6) gene can be regulated by various activating or inhibitory stimuli. This modulation involves several regulatory binding sites on the IL-6 promoter, and appears to be in general cell-specific. We have previously described that the nuclear 24 kDa isoform of fibroblast growth factor-2 (FGF-2) is able to increase IL-6 gene expression in NIH-3T3 cells. The transduction pathway involved was shown to be distinct from the extracellular mode of action of the smallest 18 kDa FGF-2 isoform. In the present study, we show that 24 kDa FGF-2-encoding vectors transfected into HeLa cells inhibit various co-transfected constructs incorporating the promoter element of the IL-6 gene and either the luciferase or the chloramphenicol acetyltransferase units. This down-regulation occurs dose-dependently with the 24 kDa FGF-2, is IL-6-promoter-specific, and does not involve an autocrine loop of the growth factor, since exogenously added FGF-2 fails to modulate the IL-6 promoter activity. Furthermore, 24 kDa FGF-2 inhibits the activity of both the co-transfected deletion mutants IL-6(-224) and IL-6(-158), and the point-mutated IL-6 promoter constructs in which the activating protein-1, nuclear factor (NF)-IL-6 and NF-kappaB elements are disrupted. We identify a responsive region to 24 kDa FGF-2 between positions -158 and -109 on the IL-6 promoter, which notably contains a retinoblastoma control element.
 ...
PMID:Inhibition of interleukin-6 promoter activity by the 24 kDa isoform of fibroblast growth factor-2 in HeLa cells. 1022 75

Vascular smooth muscle cells (SMC) are major constituents of the medial layer of blood vessels and are involved in the development of atherosclerotic plaque. SMC secrete copious IL-6 under basal conditions that can be increased by cytokines such as tumor necrosis factor-alpha and interleukin-1beta (IL-1beta). The goal of our studies was to define the role of estrogen in IL-6 production by SMC. In a first series of experiments, the expression of specific messenger RNAs as well as the production of IL-6 bioactivity by rat SMC in culture could be demonstrated in basal and IL-1-stimulated conditions, but was unaffected by estrogen treatment. Different constructs containing deleted or mutated fragments of the human IL-6 promoter driving luciferase or chloramphenicol acetyltransferase reporter gene were then transiently transfected in these cells. A significant basal activity that was increased 2- to 4-fold after IL-1beta stimulation was observed with the total IL-6 promoter. Deletion analysis indicated that the -158/+11 region containing activator protein-1 and cAMP response element sites was apparently the minimal region of IL-6 promoter to confer both constitutive and IL-1-inducible activities. Site-directed mutagenesis experiments suggest that basal activity is dependent upon the promoter sequence -158 to -112 containing the nuclear factor (NF)-IL6(-153) and Sp1 sites, whereas IL-1beta stimulation would depend on the residual -112 nucleotides containing NF-IL6(-75) and NF-kappaB sites. In contrast to the down-regulation of IL-6 expression by estrogen described in osteoblasts, ethinyl estradiol as well as 17beta-estradiol did not influence stimulated IL-6 activity in our experimental conditions whatever the construct tested, even when either estrogen receptor alpha or beta was overexpressed. Thus, the atheroprotective properties of estrogen are probably not mediated through the regulation of IL-6 production by SMC.
 ...
PMID:Expression of the interleukin-6 gene is constitutive and not regulated by estrogen in rat vascular smooth muscle cells in culture. 1034 80

The rat serine protease inhibitor (Spi) 2 gene family includes both positive (Spi 2.2) and negative (Spi 2.1) acute phase reactants, facilitating modeling of regulation of hepatic acute phase response (APR). To examine the role of signal transducer and activation of transcription (STAT) proteins in the divergent regulation of these model genes after induction of APR, we evaluated the proximal promoters of the genes, focusing on STAT binding sites contained in these promoter elements. Induction of APR by turpentine injection includes activation of a STAT3 complex that can bind to a gamma-activated sequence (GAS) in the Spi 2.2 gene promoter, although the Spi 2.2 GAS site can bind STAT1 or STAT5 as well. To create an in vitro model of APR, primary hepatocytes were treated with combinations of cytokines and hormones to mimic the hormonal milieu of the whole animal after APR induction. Incubation of primary rat hepatocytes with interleukin (IL)-6, a critical APR cytokine, leads to activation of STAT3 and a 28-fold induction of a chloramphenicol acetyltransferase reporter construct containing the -319 to +85 region of the Spi 2.2 promoter. This suggests the turpentine-induced increase of Spi 2.2 is mediated primarily by IL-6. In contrast, although turpentine treatment reduces Spi 2.1 mRNA in vivo and IL-6 does not increase Spi 2.1 mRNA in primary rat hepatocytes, treatment of hepatocytes with IL-6 results in a 5. 4-fold induction of Spi 2.1 promoter activity mediated through the paired GAS elements in this promoter. Differential regulation of Spi 2.1 and 2.2 genes is due in part to differences in the promoters of these genes at the GAS sites. IL-6 alone fails to reproduce the pattern of rat Spi 2 gene expression that results from turpentine-induced inflammation.
 ...
PMID:Regulation of Spi 2.1 and 2.2 gene expression after turpentine inflammation: discordant responses to IL-6. 1036


<< Previous 1 2 3 4 Next >>