scholarly journals Urokinase upregulates matrix metalloproteinase-9 expression in THP-1 monocytes via gene transcription and protein synthesis

2002 ◽  
Vol 367 (3) ◽  
pp. 833-839 ◽  
Author(s):  
Mikhail MENSHIKOV ◽  
Eugenia ELIZAROVA ◽  
Karina PLAKIDA ◽  
Angelika TIMOFEEVA ◽  
Georgy KHASPEKOV ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Matrix Metalloproteinase ◽  
Gene Transcription ◽  
Proteolytic Enzymes ◽  
Protein Biosynthesis ◽  
Reverse Transcription Pcr ◽  
Mmp9 Expression ◽  
Type Plasminogen Activator ◽  
Cell Incubation ◽  
Regulation Of Activity

Urokinase-type plasminogen activator (uPA) is suggested to exert its proliferatory, migratory and invasive action through binding with its membrane receptor, promoting pericellular proteolysis and mediating cell signal transduction. One of the possible actions of urokinase can be related to the regulation of activity and/or the expression of proteolytic enzymes participating in extracellular matrix degradation. In the present study, the role of uPA in regulating matrix metalloproteinase (MMP) expression and release by the monocyte cell line THP-1 was investigated. Recombinant uPA induced the release of MMP9/gelatinase B, as detected by zymography and Western blotting, and this release was abolished by actinomycin D and cycloheximide (inhibitors of DNA transcription and protein synthesis) and partially suppressed by monensin (an inhibitor of secretion). Proteolytically inactive urokinase with substitution of His204 for Gln was able to reproduce about 70% of the effect induced by the wild-type recombinant uPA. The reverse transcription-PCR and Northern blot data indicated that the action of r-uPA on THP-1 cells resulted in formation of MMP9 mRNA, which depended on time, within 6—48h, of the cell incubation with r-uPA. These results suggest that urokinase upregulates MMP9 expression in monocytes via MMP9 gene transcription and protein biosynthesis.

Modulation of Urokinase-type Plasminogen Activator Gene Expression by Inflammatory Cytokines in Human pre-B Lymphoma Cell Line RC-K8

1995 ◽  
Vol 74 (06) ◽  
pp. 1511-1515 ◽  
Author(s):  
Kenji Niiya ◽  
Masahiro Shinbo ◽  
Tetsuo Ozawa ◽  
Yumiko Hayakawa ◽  
Nobuo Sakuragawa
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Plasminogen Activator ◽  
Inflammatory Cytokines ◽  
Gene Transcription ◽  
De Novo ◽  
B Lymphoma ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Upa Mrna

SummaryWe examined the effects of inflammatory cytokines, such as interleukin-lα (IL-lα), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ) and lipopolysaccharide (LPS), on the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human pre-B lymphoma cells. Recombinant IL-1α, recombinant IL-1β and LPS but not recombinant IL-6, recombinant TNFα and TGFβ dose-dependently increased uPA accumulation in the conditioned medium. Northern blot analysis revealed that uPA mRNA levels rapidly increased with a peak induction at 2 h after stimulation with IL-lα and IL-1β, but uPA mRNA increase by LPS began at 9 h after stimulation and the increase was maintained until the experiment ended at 24 h. These responses were independent of de novo synthesis, rather amplified in the presence of a protein synthesis inhibitor. The effects by IL-1α and IL-1β were prevented by addition of anti-IL-1α and anti-IL-1β neutralizing antibodies, respectively. In contrast, both antibodies did not prevent LPS-induced uPA gene expression. Therefore, it is unlikely that the effect by LPS is through induction of IL-1. Both IL-1α and IL-1 β rapidly activated uPA gene transcription, but not increased stability of uPA mRNA. These results suggest that both IL-1α and IL-1 β cause a rapid activation of uPA gene transcription in which de novo protein synthesis is not required and that LPS induces uPA gene expression independently of the IL-1 pathway. These modulations of uPA production by inflammatory mediators may be implicated in tumor growth and metastasis.

scholarly journals Shiga Toxin 2a Binds to Complement Components C3b and C5 and Upregulates Their Gene Expression in Human Cell Lines

Toxins ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 8
Author(s):  
Sára Kellnerová ◽  
Sneha Chatterjee ◽  
Rafael Bayarri-Olmos ◽  
Louise Justesen ◽  
Heribert Talasz ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cell Lines ◽  
Gene Transcription ◽  
Specific Binding ◽  
Enterohemorrhagic Escherichia Coli ◽  
Complement Components ◽  
Western Blots ◽  
Complement Proteins ◽  
Uremic Syndrome ◽  
Complement Gene

Enterohemorrhagic Escherichia coli (EHEC) infections can cause EHEC-associated hemolytic uremic syndrome (eHUS) via its main virulent factor, Shiga toxins (Stxs). Complement has been reported to be involved in the progression of eHUS. The aim of this study was to investigate the interactions of the most effective subtype of the toxin, Stx2a, with pivotal complement proteins C3b and C5. The study further examined the effect of Stx2a stimulation on the transcription and synthesis of these complement proteins in human target cell lines. Binding of Stx2a to C3b and C5 was evaluated by ELISA. Kidney and gut cell lines (HK-2 and HCT-8) were stimulated with varied concentrations of Stx2a. Subsequent evaluation of complement gene transcription was studied by real-time PCR (qPCR), and ELISAs and Western blots were performed to examine protein synthesis of C3 and C5 in supernatants and lysates of stimulated HK-2 cells. Stx2a showed a specific binding to C3b and C5. Gene transcription of C3 and C5 was upregulated with increasing concentrations of Stx2a in both cell lines, but protein synthesis was not. This study demonstrates the binding of Stx2a to complement proteins C3b and C5, which could potentially be involved in regulating complement during eHUS infection, supporting further investigations into elucidating the role of complement in eHUS pathogenesis.

scholarly journals 1202. Subinhibitory Concentrations of Omadacycline Inhibit Staphylococcus aureus Hemolytic Activity in Vitro

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S622-S623
Author(s):  
Alisa W Serio ◽  
S Ken Tanaka ◽  
Kelly Wright ◽  
Lynne Garrity-Ryan
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Synthesis ◽  
Virulence Factors ◽  
Hemolytic Activity ◽  
Protein Biosynthesis ◽  
The United States ◽  
Aureus Strain ◽  
Protein Synthesis Inhibitors ◽  
Subinhibitory Concentrations

Abstract Background In animal models of Staphylococcus aureus infection, α-hemolysin has been shown to be a key virulence factor. Treatment of S. aureus with subinhibitory levels of protein synthesis inhibitors can decrease α-hemolysin expression. Omadacycline, a novel aminomethylcycline antibiotic in the tetracycline class of bacterial protein biosynthesis inhibitors, is approved in the United States for treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This study was performed to determine the durability of inhibition and effect of subinhibitory concentrations of omadacycline on S. aureus hemolytic activity. Methods All experiments used the methicillin-sensitive S. aureus strain Wood 46 (ATCC 10832), a laboratory strain known to secrete high levels of α-hemolysin. Minimum inhibitory concentrations (MICs) of omadacycline and comparator antibiotics (tetracycline, cephalothin, clindamycin, vancomycin, linezolid) were determined. Growth of S. aureus with all antibiotics was determined and the percentage of hemolysis assayed. “Washout” experiments were performed with omadacycline only. Results S. aureus cultures treated with 1/2 or 1/4 the MIC of omadacycline for 4 hours showed hemolysis units/108 CFU of 47% and 59% of vehicle-treated cultures, respectively (Fig. 1A, 1B). In washout experiments, treatment with as little as 1/4 the MIC of omadacycline for 1 hour decreased the hemolysis units/108 CFU by 60% for 4 hours following removal of the drug (Table 1). Figure 1 Table 1 Conclusion Omadacycline inhibited S. aureus hemolytic activity in vitro at subinhibitory concentrations and inhibition was maintained for ≥ 4 hours after removal of extracellular drug (Fig. 2). The suppression of virulence factors throughout the approved omadacycline dosing interval, in addition to the in vitro potency of omadacycline, may contribute to the efficacy of omadacycline for ABSSSI and CABP due to virulent S. aureus. This finding may apply to other organisms and other virulence factors that require new protein synthesis to establish disease. Figure 2 Disclosures Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) S. Ken Tanaka, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Lynne Garrity-Ryan, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder)

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

Tu1927 Matrix Metalloproteinase 9 (MMP9) Expression in Ulcerative Colitis Is Associated With Histologic Score of Disease Severity

2016 ◽  
Vol 150 (4) ◽  
pp. S979-S980
Author(s):  
William Sandborn ◽  
Scott Lee ◽  
Erik G. Huntzicker ◽  
Guang Chen ◽  
Victoria Smith ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Matrix Metalloproteinase ◽  
Disease Severity ◽  
Matrix Metalloproteinase 9 ◽  
Mmp9 Expression ◽  
Metalloproteinase 9

How matrix metalloproteinase (MMP)-9 (rs3918242) polymorphism affects MMP-9 serum concentration and associates with autism spectrum disorders: A case-control study in Iranian population

2021 ◽  
pp. 1-7
Author(s):  
Javid Rezaei Lord ◽  
Farhad Mashayekhi ◽  
Zivar Salehi
Keyword(s):  
Serum Concentration ◽  
Matrix Metalloproteinase ◽  
Serum Levels ◽  
Autism Spectrum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mmp9 Expression ◽  
Relationship Of ◽  
The Relationship ◽  
Metalloproteinase 9 ◽  
Control Study

Abstract The aim of this project was to evaluate the relationship of matrix metalloproteinase-9 (MMP-9) genetic variation and its serum concentration with autism spectrum disorder (ASD). One hundred ASD and 120 controls were enrolled in this study. Genomic DNA was extracted from blood and MMP-9 polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism and serum levels were measured by enzyme-linked immunosorbent assay. The frequencies of CC, CT, and TT genotypes were 72%, 26%, and 2% in controls and 31%, 57%, and 12% in ASD, respectively. The frequencies of C and T alleles in ASD were 59.5% and 40.5%, and controls were 86% and 14%, respectively. There is a significant increase in serum MMP-9 levels in ASD as compared to controls. We have also shown that TT genotype is significantly associated with increase serum MMP-9 levels in patients (TT, CT, and CC serum levels were 91.77 ± 10.53, 70.66 ± 7.21, and 38.66 ± 5.52 and in controls were 55.55 ± 11.39, 42.66 ± 7.85, and 30.55 ± 6.34 ng/ml, respectively). It is concluded that there is a significant association between rs3918242 MMP-9 polymorphism and its serum concentration with autism. We also suggest that TT genotype is associated with increased MMP9 expression and may be a risk factor for ASD.

Coordinate changes in heat shock element-binding activity and HSP70 gene transcription rates in human cells

1988 ◽  
Vol 8 (11) ◽  
pp. 4736-4744
Author(s):  
D D Mosser ◽  
N G Theodorakis ◽  
R I Morimoto
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Heat Shock ◽  
Gene Transcription ◽  
Elevated Temperatures ◽  
Binding Activity ◽  
Heat Shock Gene ◽  
Hsp70 Gene ◽  
Heat Shock Element ◽  
Amino Acid Analogs

Activation of human heat shock gene transcription by heat shock, heavy metal ions, and amino acid analogs required the heat shock element (HSE) in the HSP70 promoter. Both heat shock- and metal ion-induced HSP70 gene transcription occurred independently of protein synthesis, whereas induction by amino acid analogs required protein synthesis. We identified a HSE-binding activity from control cells which was easily distinguished by a gel mobility shift assay from the stress-induced HSE-binding activity which appeared following heat shock or chemically induced stress. The kinetics of HSP70 gene transcription paralleled the rapid appearance of stress-induced HSE-binding activity. During recovery from heat shock, both the rate of HSP70 gene transcription and stress-induced HSE-binding activity levels declined and the control HSE-binding activity reappeared. The DNA contacts of the control and stress-induced HSE-binding activities deduced by methylation interference were similar but not identical. While stable complexes with HSE were formed with extracts from both control and stressed cells in vitro at 25 degrees C, only the stress-induced complex was detected when binding reactions were performed at elevated temperatures.

Influence of Neurosecretory Cells and of Corpus Allatum on Intestinal Protease Activity in the Adult Calliphora Erythrocephala MEIG

1963 ◽  
Vol 40 (2) ◽  
pp. 301-321
Author(s):  
ELLEN THOMSEN ◽  
IB MØLLER
Keyword(s):  
Protein Synthesis ◽  
Protease Activity ◽  
Proteolytic Enzymes ◽  
Specific Protein ◽  
Neurosecretory Cells ◽  
Corpus Allatum ◽  
Minor Effect ◽  
Calliphora Erythrocephala ◽  
Sugar Water ◽  
The Mean

1. The protease activity of the adult Calliphora female measured on the first 5 days after emergence was found to be highly influenced by the diet, the activity of females fed on sugar, water and meat (meat-flies) being much higher than that of females fed only on sugar and water (sugar-flies). 2. The development of the enzyme(s) was found to be controlled by the medial neurosecretory cells (m.n.c.), the mean protease activity of females deprived of their m.n.c. only amounting to one-quarter to one-third of the maximum values for the meat-flies. 3. Implantation of corpora cardiaca-allata (presumably containing m.n.c. hormone) into females without m.n.c. raised the protease activity of these significantly, showing that the influence of the implanted organs must be hormonal. 4. The corpus allatum was found to have a certain, if minor, effect on the protease activity. 5. It is concluded that in Calliphora the eating of meat exerts its effect on the production of protease mainly indirectly by causing liberation of m.n.c. hormone into the blood. 6. As proteases are themselves proteins, the effect of the m.n.c. hormone on the production of proteolytic enzymes by the gut cells must be regarded as an effect on the specific protein synthesis of these cells. There is some evidence that the m.n.c. hormone might be involved in the regulation of protein synthesis in general.

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