scholarly journals Enterohemorrhagic Escherichia coli Infection Induces Interleukin-8 Production via Activation of Mitogen-Activated Protein Kinases and the Transcription Factors NF-κB and AP-1 in T84 Cells

2002 ◽  
Vol 70 (5) ◽  
pp. 2304-2310 ◽  
Author(s):  
Stephanie Dahan ◽  
Valere Busuttil ◽  
Veronique Imbert ◽  
Jean-Francois Peyron ◽  
Patrick Rampal ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcription Factors ◽  
Dna Binding ◽  
Protein Kinases ◽  
Binding Activity ◽  
Interleukin 8 ◽  
T84 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Mitogen Activated Protein

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) infections are associated with hemorrhagic colitis and the hemolytic-uremic syndrome (HUS). In vivo, elevated plasma levels of the proinflammatory cytokine interleukin-8 (IL-8) in EHEC-infected children are correlated with a high risk of developing HUS. As IL-8 gene transcription is regulated by the transcription factors NF-κB and AP-1, we analyzed the role of these factors in the regulation of IL-8 production after infection of the epithelial intestinal T84 cell line by EHEC. By 6 h of infection, EHEC had induced significant secretion of IL-8 (35.84 ± 6.76 ng/ml versus 0.44 ± 0.04 ng/ml in control cells). EHEC induced AP-1 and NF-κB activation by 3 h of infection. Moreover, the three mitogen-activated protein kinases (MAPK) (ERK1/2, p38, and JNK) were phosphorylated in EHEC-infected T84 cells concomitant with induction of AP-1 DNA binding activity, and IκB-α was phosphorylated and then degraded concomitant with induction of NF-κB DNA binding activity. Pretreatment of cells with the highly specific MEK1/2 inhibitor U0126, the p38 inhibitor SB203580, and/or the proteasome inhibitor ALLN led to inhibition of the IL-8 secretion induced in EHEC-infected T84 cells. These findings demonstrate that (i) EHEC can induce in vitro a potent proinflammatory response by secretion of IL-8 and (ii) the secretion of IL-8 is due to the involvement of MAPK, AP-1, and NF-κB signaling pathways.

scholarly journals The Afa/Dr Adhesins of Diffusely Adhering Escherichia coli Stimulate Interleukin-8 Secretion, Activate Mitogen-Activated Protein Kinases, and Promote Polymorphonuclear Transepithelial Migration in T84 Polarized Epithelial Cells

2003 ◽  
Vol 71 (3) ◽  
pp. 1068-1074 ◽  
Author(s):  
Fréderic Bétis ◽  
Patrick Brest ◽  
Véronique Hofman ◽  
Julie Guignot ◽  
Marie-Françoise Bernet-Camard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Protein Kinases ◽  
Interleukin 8 ◽  
Intestinal Cell ◽  
Proinflammatory Response ◽  
T84 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

ABSTRACT Afa/Dr diffusely adhering Escherichia coli (Afa/Dr DAEC) strains cause symptomatic urinary tract and intestinal infections. The proinflammatory effects of Afa/Dr DAEC strains in vitro have been not investigated to date. In the present study, we used confluent polarized monolayers of intestinal cell line T84 to evaluate the consequences of epithelial infection by Afa/Dr DAEC strains in terms of proinflammatory response. Polymorphonuclear leukocyte (PMNL) migration across the epithelial barrier was induced after incubation of the T84 monolayers with the wild-type Afa/Dr DAEC strain C1845 harboring the fimbrial F1845 adhesin and strain IH11128 harboring the Dr hemagglutinin, and the E. coli laboratory strain HB101 was transformed with the pSSS1 plasmid, producing Afa/Dr F1845 adhesin. PMNL migrations were correlated with a basolateral secretion of interleukin-8 by T84 cells and were abolished after incubation of epithelial cells with an anti-decay accelerating factor (DAF) antibody that recognized the short consensus repeat 3 domain of DAF (monoclonal antibody 1H4). Moreover, Afa/Dr DAEC strains induced tyrosine phosphorylation of several T84 proteins and activated the mitogen-activated protein kinases (ERK1/2 mitogen-activated protein, P38, and Jun-C kinases). These data demonstrated for the first time that, in vitro, Afa/Dr DAEC strains exert a proinflammatory signal in intestinal epithelial cells.

scholarly journals Chronic Activation of Glomerular Mitogen-Activated Protein Kinases in Dahl Salt-Sensitive Rats

2000 ◽  
Vol 11 (1) ◽  
pp. 39-46
Author(s):  
AKINORI HAMAGUCHI ◽  
SHOKEI KIM ◽  
YASUKATSU IZUMI ◽  
HIROSHI IWAO
Keyword(s):  
Protein Kinases ◽  
Binding Activity ◽  
High Salt ◽  
Glomerular Injury ◽  
High Salt Diet ◽  
Mitogen Activated Protein Kinases ◽  
Salt Diet ◽  
Dna Binding Activity ◽  
Mitogen Activated Protein ◽  
Chronic Activation

Abstract. The in vivo role of mitogen-activated protein kinases (MAPK) in the development of glomerular injury is poorly understood. In the present study, glomerular MAPK activities, including extracellular signal-regulated kinases (ERK), c-Jun NH2-terminal kinases (JNK), and transcriptional factor, activator protein-1 (AP-1) were examined in glomerular injury of salt-induced hypertensive rats. Six-week-old Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were maintained on a high-salt (8.0% NaCl) diet for 1, 5, and 10 wk. In Dahl-S rats, as shown by in-gel kinase assay, an increase in BP by a high-salt diet was followed by chronic activation of glomerular ERK and JNK, which continued until 10 wk after a high-salt diet. Western blot analysis demonstrated a significant increase in the protein expression of glomerular ERK and JNK in Dahl-S rats fed a high-salt diet. As determined by gel-mobility shift assay, ERK and JNK activations were associated with an increase in glomerular AP-1 DNA binding activity. On the other hand, in Dahl-R rats fed a high-salt diet, BP remained normal throughout the experiments. However, glomerular ERK and JNK activities and AP-1 DNA binding activity in Dahl-R rats were not affected by 1 or 5 wk of a high-salt diet, but significantly increased by 10 wk of treatment with a high-salt diet, indicating that chronic sodium overload itself stimulated glomerular ERK and JNK and AP-1 activities. These kinase activations in both Dahl-S and Dahl-R rats were accompanied by an increase in urinary protein excretion and renal growth. These observations provide the first evidence that salt-sensitive hypertension causes chronic activation of glomerular ERK and JNK, probably leading to the activation of AP-1. Thus, glomerular MAPK may be responsible for the development of salt-induced glomerular injury.

scholarly journals Bacteroides fragilis Enterotoxin Induces Sulfiredoxin-1 Expression in Intestinal Epithelial Cell Lines Through a Mitogen-Activated Protein Kinases- and Nrf2-Dependent Pathway, Leading to the Suppression of Apoptosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5383
Author(s):  
Jong Ik Jeon ◽  
Jun Ho Choi ◽  
Keun Hwa Lee ◽  
Jung Mogg Kim
Keyword(s):  
Protein Kinases ◽  
Bacteroides Fragilis ◽  
Binding Activity ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Oxidative Damages ◽  
Epithelial Cell Lines ◽  
Mitogen Activated Protein

Enterotoxigenic Bacteroides fragilis is a causative agent of colitis and secrets enterotoxin (BFT), leading to the disease. Sulfiredoxin (Srx)-1 serves to protect from oxidative damages. Although BFT can generate reactive oxygen species in intestinal epithelial cells (IECs), no Srx-1 expression has been reported in ETBF infection. In this study, we explored the effects of ETBF-produced BFT on Srx-1 induction in IECs. Treatment of IECs with BFT resulted in increased expression of Srx-1 in a time-dependent manner. BFT treatment also activated transcriptional signals including Nrf2, AP-1 and NF-κB, and the Srx-1 induction was dependent on the activation of Nrf2 signals. Nrf2 activation was assessed using immunoblot and Nrf2-DNA binding activity and the specificity was confirmed by supershift and competition assays. Suppression of NF-κB or AP-1 signals did not affect the upregulation of Srx-1 expression. Nrf2-dependent Srx-1 expression was associated with the activation of p38 mitogen-activated protein kinases (MAPKs) in IECs. Furthermore, suppression of Srx-1 significantly enhanced apoptosis while overexpression of Srx-1 significantly attenuated apoptosis during exposure to BFT. These results imply that a signaling cascade involving p38 and Nrf2 is essential for Srx-1 upregulation in IECs stimulated with BFT. Following this upregulation, Srx-1 may control the apoptosis in BFT-exposed IECs.

scholarly journals Activation of glomerular mitogen-activated protein kinases in angiotensin II-mediated hypertension.

1998 ◽  
Vol 9 (3) ◽  
pp. 372-380 ◽  
Author(s):  
A Hamaguchi ◽  
S Kim ◽  
M Yano ◽  
S Yamanaka ◽  
H Iwao
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinases ◽  
Binding Activity ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Mitogen Activated Protein Kinases ◽  
Dna Binding Activity ◽  
Induced Hypertension ◽  
Mitogen Activated Protein

The in vivo signal transduction pathway, responsible for hypertension-induced glomerular injury, remains to be clarified. In this study, the effect of angiotensin II (Ang II)-induced hypertension was examined on glomerular mitogen activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), and on glomerular transcription factors activator protein-1 (AP-1) and Sp 1. MAPK activities were determined by in-gel kinase assay. DNA binding activity of AP-1 and Sp 1 was determined by gel mobility shift assay. Continuous infusion of Ang II (1000 ng/kg per min, intravenously) to conscious rats rapidly increased BP, followed by the rapid and transient activation of glomerular p42 and p44 ERK and p46 and p55 JNK with the peak at 15 to 180 min. Glomerular AP-1 binding activity was increased 2.6-fold (P < 0.01) at 24 h after the start of Ang II infusion. Supershift analysis showed that the activated AP-1 complexes contained c-Fos and c-Jun proteins. On the other hand, glomerular Sp 1 DNA binding activity was not changed throughout 7 d of Ang II infusion. These results provided the first in vivo evidence that Ang II-induced hypertension causes the activation of glomerular ERK and JNK, leading to the activation of AP-1. Thus, ERK and JNK signaling cascades, via the activation of AP-1, may be implicated in the development of hypertension-induced glomerular injury.

scholarly journals Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication

2008 ◽  
Vol 36 (10) ◽  
pp. 3341-3353 ◽  
Author(s):  
Paul Peixoto ◽  
Yang Liu ◽  
Sabine Depauw ◽  
Marie-Paule Hildebrand ◽  
David W. Boykin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Activity ◽  
Direct Inhibition ◽  
Selective Binding ◽  
Dna Binding Activity

scholarly journals Overexpression of mitogen-activated protein kinase (ERK1) enhances T- cell cytokine gene expression: role of AP1, NF-AT, and NF-KB

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2470-2477 ◽  
Author(s):  
JH Park ◽  
L Levitt
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Dna Binding ◽  
Map Kinase ◽  
Binding Activity ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Dna Binding Activity ◽  
Mitogen Activated Protein

Abstract Transfected Jurkat cells overexpressing extracellular signal-regulated kinase (ERK1), also referred to as mitogen-activated protein (MAP) kinase, were selected by Western blotting assay using anti-ERK1 and antiphosphotyrosine antibodies in combination with a functional MAP kinase assay. We then asked whether enhanced ERK1 expression had any effect on induction of T-cell cytokine genes. The results show that overexpression of ERK1 enhances expression of T-cell interleukin-2 (IL- 2), IL-3, and granulocyte-macrophage colony-stimulating factor mRNA; no change was seen in expression of the alpha-actin gene. DNA-binding activities of the transcription factors AP1, NF-AT, and NF-kB were specifically increased twofold to fourfold in ERK1-overexpressing clones relative to nontransformed or vector-transformed cells, whereas no enhancement of CK1-CK2 protein DNA binding activity was detected after ERK1 overexpression. Additionally, increased NF-AT DNA binding activity was associated with functional enhancement of NF-AT transactivating activity in ERK1-overexpressing cells. These results provide direct evidence for the role of MAP kinase in the regulation of cytokine gene expression and indicate that such regulation is likely mediated through the enhanced DNA binding activity of specific nuclear transcription factors.

Ozone-induced IL-8 expression and transcription factor binding in respiratory epithelial cells

1997 ◽  
Vol 272 (3) ◽  
pp. L504-L511 ◽  
Author(s):  
I. Jaspers ◽  
E. Flescher ◽  
L. C. Chen
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Epithelial Cells ◽  
Inflammatory Cells ◽  
Binding Activity ◽  
Ozone Exposure ◽  
Air Exposure ◽  
Dna Binding Activity ◽  
Nf Kappab

Ozone, one of the most reactive oxidant gases to which humans are routinely exposed, induces inflammation in the lower airways. The airway epithelium is one of the first targets that inhaled ozone will encounter, but its role in airway inflammation is not well understood. Expression of inducible genes involved in the inflammatory response, such as interleukin (IL)-8, is controlled by transcription factors. Expression of the IL-8 gene is regulated by the transcription factors nuclear factor (NF)-kappaB, NF-IL-6, and possibly activator protein-1 (AP-1). Type II-like epithelial cells (A549) were grown on a collagen-coated membrane and exposed in vitro to 0.1 ppm ozone or air. Exposure to ozone induced DNA-binding activity of NF-kappaB, NF-IL-6, and AP-1. IL-8 mRNA and IL-8 protein levels were also increased after ozone exposure. These results link ozone-induced DNA-binding activity of transcription factors and the production of IL-8 by epithelial cells thus demonstrating a potential cellular cascade resulting in the recruitment of inflammatory cells into the airway lumen.

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