scholarly journals Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes: transcriptional inhibition by interferon-γ

1995 ◽  
Vol 310 (3) ◽  
pp. 751-755 ◽  
Author(s):  
M A Cassatella ◽  
S Gasperini ◽  
F Calzetti ◽  
P P McDonald ◽  
G Trinchieri
Keyword(s):  
Gene Expression ◽  
Interferon Γ ◽  
Interleukin 8 ◽  
Polymorphonuclear Leucocytes ◽  
Mrna Accumulation ◽  
Ifn Gamma ◽  
Potent Inducer ◽  
Transcriptional Inhibition ◽  
Human Granulocytes ◽  
New Protein

We recently showed that lipopolysaccharide (LPS) is a potent inducer of interleukin-8 (IL-8) expression in human polymorphonuclear leucocytes (PMN), at the level of both mRNA and protein, and that interferon-gamma (IFN gamma) inhibits IL-8 mRNA accumulation in stimulated PMN. To further define the molecular basis of the regulation of IL-8 gene expression in PMN, we investigated the effects of LPS and IFN gamma at both the transcriptional and post-transcriptional levels. As determined by Northern blot analysis, new protein synthesis was not required for the induction of IL-8 mRNA expression by LPS. Neither did the half-life of IL-8 mRNA in LPS-treated PMN differ from that observed in untreated cells. However, nuclear run-on analysis revealed that LPS increased the transcription of the IL-8 and IL-1 beta genes and that, in LPS-activated cells, IFN gamma markedly inhibited the rate of IL-8 gene transcription, but not that of IL-1 beta. IFN gamma did not affect IL-8 mRNA stability in LPS-treated PMN, indicating that the cytokine does not regulate LPS-induced IL-8 gene expression through post-transcriptional events. These results provide the first evidence that human granulocytes can actively transcribe the IL-8 gene, and that transcriptional inhibition is the mechanism by which IFN gamma inhibits IL-8 gene expression in PMN.

scholarly journals Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 537-542
Author(s):  
MC Bosco ◽  
GL Gusella ◽  
I Espinoza-Delgado ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Ifn Gamma ◽  
Potent Inducer

Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time- dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL- 8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.

scholarly journals Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 537-542 ◽  
Author(s):  
MC Bosco ◽  
GL Gusella ◽  
I Espinoza-Delgado ◽  
DL Longo ◽  
L Varesio
Keyword(s):  
Gene Expression ◽  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Interleukin 8 ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Ifn Gamma ◽  
Potent Inducer

Abstract Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is produced in response to several stimuli. Because monocytic cells are important producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent inducer of activation and differentiation of mononuclear phagocytes, affected IL-8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA expression that was upregulated by IFN-gamma in a dose- and time- dependent manner and via a protein-synthesis-dependent process in the human monocytic cell line U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on experiments showed that the IL- 8 gene was transcriptionally active in control cells and that IFN-gamma did not enhance the transcriptional activity. The increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the mRNA and, therefore, controlled primarily at a posttranscriptional level. These results represent the first evidence that IFN-gamma upregulates IL-8 gene expression in cells of the monocytic lineage, and show the involvement of posttranscriptional mechanisms in the induction of IL-8 mRNA.

Probiotic Therapy in the Prevention of Pouchitis Onset: Decreased Interleukin-1β, Interleukin-8, and Interferon-γ Gene Expression

2005 ◽  
Vol 11 (5) ◽  
pp. 447-454 ◽  
Author(s):  
Karen M Lammers ◽  
Athanasios Vergopoulos ◽  
Nina Babel ◽  
Paolo Gionchetti ◽  
Fernando Rizzello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interferon Γ ◽  
Interleukin 8 ◽  
Interleukin 1Β

scholarly journals Interferon-γ-dependent stimulation of human involucrin gene expression: STAT1 (signal transduction and activators of transcription 1) protein activates involucrin promoter activity

1999 ◽  
Vol 344 (3) ◽  
pp. 797-802 ◽  
Author(s):  
Hidetoshi TAKAHASHI ◽  
Kazuhiro ASANO ◽  
Satoshi NAKAMURA ◽  
Akemi ISHIDA-YAMAMOTO ◽  
Hajime IIZUKA
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Promoter Activity ◽  
Expression Vector ◽  
Human Keratinocytes ◽  
Interferon Γ ◽  
Luciferase Reporter ◽  
Potent Inducer ◽  
Ifn Γ ◽  
Involucrin Promoter

Involucrin is one of the precursor proteins of the cornified cell envelope of keratinocytes, and is expressed during the later stages of keratinocyte differentiation. Interferon-γ (IFN-γ), a pleiotropic cytokine with anti-proliferative and immunomodulatory activities, is also a potent inducer of squamous differentiation. Using cultured normal human keratinocytes (NHK cells) and simian virus 40-transformed human keratinocytes (SVHK cells), we investigated the effects of IFN-γ on involucrin gene expression. Expression of involucrin was increased by about 3-fold after treating NHK cells with IFN-γ (100 units/ml). Northern blot analyses revealed that IFN-γ increased the expression of involucrin mRNA. The fragment +42 to -2463 in the 5ʹ-flanking region of the human involucrin gene was subcloned into a luciferase reporter vector and the construct (p2463Luc) was transfected into SVHK cells. p2463Luc produced a 3-fold increase in luciferase activity after IFN-γ treatment. Sequence analysis detected two putative IFN-γ-responsive regions [G1 (positions -883 to -874) and G2 (-784 to -775)]. Deletion analyses of the p2463Luc vector revealed that the G1 region is critical for the IFN-γ-dependent up-regulation of the involucrin gene. Gel-shift analyses revealed that STAT1 (signal transduction and activators of transcription 1) protein bound to the G1 region and that involucrin promoter activity was augmented by transfection of a STAT1 expression vector in the presence of IFN-γ. In contrast, transfection of a STAT1 dominant-negative expression vector suppressed the IFN-γ-dependent up-regulation of involucrin promoter activity. These results indicate that IFN-γ stimulates expression of the human involucrin gene via the G1 (-883 to -874) region of the involucrin gene promoter.

Mechanism of dexamethasone-mediated interleukin-8 gene suppression in cultured airway epithelial cells

2001 ◽  
Vol 280 (1) ◽  
pp. L107-L115 ◽  
Author(s):  
Mary Mann-Jong Chang ◽  
Maya Juarez ◽  
Dallas M. Hyde ◽  
Reen Wu
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Epithelial Cells ◽  
Actinomycin D ◽  
Airway Epithelial Cells ◽  
Interleukin 8 ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
New Protein

The effects of dexamethasone, a glucocorticoid analog, on interleukin 8 (IL-8) gene expression were studied in cultures of primary human tracheobronchial epithelial cells and an immortalized human bronchial epithelial cell line, HBE1 cells. Dexamethasone inhibited IL-8 mRNA and protein expression in a concentration- and time-dependent manner. The inhibition did not occur at the transcriptional level since both nuclear run-on activity and IL-8 promoter-reporter gene expression assay revealed no significant effect. Instead, there was a change in IL-8 mRNA stability in dexamethasone-treated cultures. Under actinomycin D treatment, IL-8 mRNA was quite stable in dexamethasone-depleted cultures, while in dexamethasone-pretreated cultures, IL-8 message was rapidly degraded within the first hour, then leveled off. When dexamethasone and actinomycin D were added simultaneously to dexamethasone-depleted cultures, IL-8 mRNA remained rather stable. When cycloheximide was used to inhibit new protein synthesis, dexamethasone-dependent inhibition was not observed. These results suggest that a posttranscriptional mechanism, which requires dexamethasone-dependent new protein synthesis, is involved in the regulation of IL-8 mRNA by dexamethasone in airway epithelial cells.

scholarly journals Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes.

1994 ◽  
Vol 180 (4) ◽  
pp. 1367-1374 ◽  
Author(s):  
C H Chang ◽  
J D Fontes ◽  
M Peterlin ◽  
R A Flavell
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Inducible Expression ◽  
Class Ii Transactivator ◽  
Ifn Gamma ◽  
Histocompatibility Complex ◽  
New Protein

The class II transactivator (CIITA) has been shown to be required for major histocompatibility complex (MHC) class II gene expression in B cells and its deficiency is responsible for a hereditary MHC class II deficiency. Here we show that CIITA is also involved in the inducible expression of class II genes upon interferon gamma (IFN-gamma) treatment. The expression of CIITA is also inducible with IFN-gamma before the induction of MHC class II mRNA. In addition, CIITA mRNA expression does not require new protein synthesis, although new protein synthesis is necessary for the transcription of class II. This suggests that synthesis of new CIITA protein may be essential to induce class II gene expression. We also showed that the JAK1 protein tyrosine kinase activity is required to induce the expression of CIITA upon IFN-gamma stimulation. This finding indicates that CIITA is part of the signaling cascade from the IFN-gamma receptor to the activation of class II genes. In addition, the expression of CIITA is sufficient to activate class II genes in the absence of IFN-gamma stimulation suggesting that CIITA is the major regulatory factor for the inducible expression of class II genes. Together, these data suggest that CIITA is the IFN-inducible cycloheximide sensitive factor previously shown to be required for the induction of MHC class II gene expression.

scholarly journals Interaction of 7SK with the Smn complex modulates snRNP production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Changhe Ji ◽  
Jakob Bader ◽  
Pradhipa Ramanathan ◽  
Luisa Hennlein ◽  
Felix Meissner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Fine Tuning ◽  
Global Changes ◽  
Functional Association ◽  
Transcriptional Inhibition ◽  
Smn Complex ◽  
Core Components

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

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