scholarly journals Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2733-2740 ◽  
Author(s):  
K Yoshimura ◽  
RG Crystal
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Gene Transcription ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Leukemia Cell Line ◽  
Human Neutrophil Elastase ◽  
Mrna Levels ◽  
Mrna Transcript ◽  
Lineage Differentiation

Abstract Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12- myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation.

scholarly journals Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2733-2740
Author(s):  
K Yoshimura ◽  
RG Crystal
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Gene Transcription ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Leukemia Cell Line ◽  
Human Neutrophil Elastase ◽  
Mrna Levels ◽  
Mrna Transcript ◽  
Lineage Differentiation

Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12- myristate 13-acetate (PMA), HL-60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation.

scholarly journals Flavonoids as inhibitors of human neutrophil elastase

2021 ◽  
Vol 36 (1) ◽  
pp. 1016-1028
Author(s):  
Katarzyna Jakimiuk ◽  
Jakub Gesek ◽  
Atanas G. Atanasov ◽  
Michał Tomczyk
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase

Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones

1994 ◽  
Vol 37 (26) ◽  
pp. 4538-4553 ◽  
Author(s):  
Michael R. Angelastro ◽  
Larry E. Baugh ◽  
Philippe Bey ◽  
Joseph P. Burkhart ◽  
Teng-Man Chen ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase ◽  
Orally Active

Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells

2004 ◽  
Vol 287 (4) ◽  
pp. L764-L773 ◽  
Author(s):  
Loretta Sparkman ◽  
Vijayakumar Boggaram
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Gene Transcription ◽  
Mrna Stability ◽  
Inflammatory Responses ◽  
Lung Epithelial Cells ◽  
Mrna Levels ◽  
Lung Epithelial

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.

Optimisation of a human neutrophil elastase assay and investigation of the effect of sesquiterpene lactones

Biologicals ◽  
2005 ◽  
Vol 33 (3) ◽  
pp. 175-184 ◽  
Author(s):  
Karin Schorr ◽  
Anita Rott ◽  
FernandoBatista Da Costa ◽  
Irmgard Merfort
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Sesquiterpene Lactones ◽  
Human Neutrophil Elastase

scholarly journals Feedback Inhibition of Human Scavenger Receptor Class B Type I Gene Expression by Glucocorticoid in Adrenal and Ovarian Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3214-3224 ◽  
Author(s):  
Sofia Mavridou ◽  
Maria Venihaki ◽  
Olga Rassouli ◽  
Christos Tsatsanis ◽  
Dimitris Kardassis
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Feedback Inhibition ◽  
Steroid Hormone ◽  
Scavenger Receptor ◽  
Type I ◽  
Mrna Levels ◽  
Ovarian Cells ◽  
Scavenger Receptor Class ◽  
Class B

Scavenger receptor class B type I (SR-BI) facilitates the reverse transport of excess cholesterol from peripheral tissues to the liver via high-density lipoproteins. In steroidogenic tissues, SR-BI supplies cholesterol for steroid hormone production. We show here that the transcription of the human SR-BI gene is subject to feedback inhibition by glucocorticoid in adrenal and ovarian cells. SR-BI mRNA levels were increased in adrenals from corticosterone-insufficient Crh−/− mice, whereas corticosterone replacement by oral administration inhibited SR-BI gene expression in these mice. SR-BI mRNA levels were increased in adrenals from wild-type mice treated with metyrapone, a drug that blocks corticosterone synthesis. Experiments in adrenocortical H295R and ovarian SKOV-3 cells using cycloheximide and siRNA-mediated gene silencing revealed that glucocorticoid-mediated inhibition of SR-BI gene transcription requires de novo protein synthesis and the glucocorticoid receptor (GR). No direct binding of GR to the SR-BI promoter could be demonstrated in vitro and in vivo, suggesting an indirect mechanism of repression of SR-BI gene transcription by GR in adrenal cells. Deletion analysis established that the region of the human SR-BI promoter between nucleotides −201 and −62 is sufficient to mediate repression by glucocorticoid. This region contains putative binding sites for transcriptional repressors that could play a role in SR-BI gene regulation in response to glucocorticoid. In summary, this is the first report showing that glucocorticoid suppress SR-BI expression suggesting that steroidogenic tissues maintain steroid hormone homeostasis by prohibiting SR-BI-mediated high-density lipoprotein cholesterol uptake when the endogenous levels of glucocorticoid are elevated.

scholarly journals Elastase as a marker for neutrophilic myeloid cells.

1984 ◽  
Vol 32 (4) ◽  
pp. 389-394 ◽  
Author(s):  
J A Kramps ◽  
P van der Valk ◽  
M M van der Sandt ◽  
J Lindeman ◽  
C J Meijer
Keyword(s):  
Cell Lines ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Myeloid Cells ◽  
Hematopoietic Cell ◽  
Human Neutrophil Elastase ◽  
Specific Marker ◽  
Neoplastic Cells ◽  
Myeloproliferative Diseases ◽  
Myelomonocytic Leukemia

The immunohistochemical results obtained with antibodies directed against human neutrophil elastase is described. It was found that neutrophil elastase can be used as a specific marker of cells of the neutrophilic lineage. In normal hematopoietic cell preparations, only promyelocytes and more differentiated myeloid cells stain positive for elastase. In acute or chronic myeloid and myelomonocytic leukemia, the same neutrophil myeloid cells stain positive, whereas neoplastic cells of the monocytoid line are negative. Using elastase in conjunction with other markers, it is possible to differentiate easily the involvement of different cell lines in myeloproliferative diseases.

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