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 Bacteroides fragilis Enterotoxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 through Mitogen-Activated Protein Kinases and a Tyrosine Kinase-Regulated Nuclear Factor-κB Pathway

2004 ◽  
Vol 72 (10) ◽  
pp. 5832-5839 ◽  
Author(s):  
Shaoguang Wu ◽  
Jan Powell ◽  
Nes Mathioudakis ◽  
Sheryl Kane ◽  
Ellen Fernandez ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Bacteroides Fragilis ◽  
Nuclear Factor Κb ◽  
Interleukin 8 ◽  
Biologically Active ◽  
Nuclear Factor ◽  
Intestinal Epithelial ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

ABSTRACT Enterotoxigenic Bacteroides fragilis (ETBF) secretes a 20-kDa metalloprotease toxin termed B. fragilis toxin (BFT). ETBF disease in animals is associated with an acute inflammatory response in the intestinal mucosa, and lethal hemorrhagic colitis may occur in rabbits. In this study, we confirmed recent reports (J. M. Kim, Y. K. Oh, Y. J. Kim, H. B. Oh, and Y. J. Cho, Clin. Exp. Immunol. 123:421-427, 2001; L. Sanfilippo, C. K. Li, R. Seth, T. J. Balwin, M. J. Menozzi, and Y. R. Mahida, Clin. Exp. Immunol. 119:456-463, 2000) that purified BFT stimulates interleukin-8 (IL-8) secretion by human intestinal epithelial cells (HT29/C1 cells) and demonstrate that stimulation of IL-8 production is dependent on biologically active BFT and independent of serum. Induction of IL-8 mRNA expression occurs rapidly and ceases by 6 h after BFT treatment, whereas IL-8 secretion continues to increase for at least 18 h. Our data suggest that BFT-stimulated IL-8 secretion involves tyrosine kinase-dependent activation of nuclear factor-κB (NF-κB) as well as activation of the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-related kinase. Simultaneous activation of NF-κB and MAPKs appears necessary for secretion of IL-8 by HT29/C1 cells treated with BFT.

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 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 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 Silencing of WIPK and SIPK Mitogen-Activated Protein Kinases Reduces Tobacco mosaic virus Accumulation But Permits Systemic Viral Movement in Tobacco Possessing the N Resistance Gene

2010 ◽  
Vol 23 (8) ◽  
pp. 1032-1041 ◽  
Author(s):  
Michie Kobayashi ◽  
Shigemi Seo ◽  
Katsuyuki Hirai ◽  
Ayako Yamamoto-Katou ◽  
Shinpei Katou ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Resistance Gene ◽  
Protein Kinases ◽  
N Gene ◽  
Dependent Manner ◽  
Mitogen Activated Protein Kinases ◽  
Systemic Spread ◽  
Mitogen Activated Protein ◽  
Viral Accumulation

Infection of tobacco cultivars possessing the N resistance gene with Tobacco mosaic virus (TMV) results in confinement of the virus by necrotic lesions at the infection site. Although the mitogen-activated protein kinases WIPK and SIPK have been implicated in TMV resistance, evidence linking them directly to disease resistance is, as yet, insufficient. Viral multiplication was reduced slightly in WIPK- or SIPK-silenced plants but substantially in WIPK/SIPK-silenced plants, and was correlated with an increase in salicylic acid (SA) and a decrease in jasmonic acid (JA). Silencing of WIPK and SIPK in a tobacco cultivar lacking the N gene did not inhibit viral accumulation. The reduction in viral accumulation was attenuated by expressing a gene for an SA-degrading enzyme or by exogenously applying JA. Inoculation of lower leaves resulted in the systemic spread of TMV and formation of necrotic lesions in uninoculated upper leaves. These results suggested that WIPK and SIPK function to negatively regulate local resistance to TMV accumulation, partially through modulating accumulation of SA and JA in an N-dependent manner, but positively regulate systemic resistance.

scholarly journals Bacteroides fragilis Enterotoxin Upregulates Matrix Metalloproteinase-7 Expression through MAPK and AP-1 Activation in Intestinal Epithelial Cells, Leading to Syndecan-2 Release

2021 ◽  
Vol 22 (21) ◽  
pp. 11817
Author(s):  
Jong Ik Jeon ◽  
Keun Hwa Lee ◽  
Jung Mogg Kim
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Bacteroides Fragilis ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Concentration Dependent Manner ◽  
Activation Of Transcription ◽  
Mitogen Activated Protein ◽  
Matrix Metalloproteinase 7

Bacteroides fragilis enterotoxin (BFT) produced by enterotoxigenic B. fragilis (ETBF) causes colonic inflammation. BFT initially contacts intestinal epithelial cells (IECs) and affects the intestinal barrier. Although molecular components of the gut epithelial barrier such as metalloproteinase-7 (MMP-7) and syndecan-2 are known to be associated with inflammation, little has been reported about MMP-7 expression and syndecan-2 shedding in response to ETBF infection. This study explores the role of BFT in MMP-7 induction and syndecan-2 release in IECs. Stimulating IECs with BFT led to the induction of MMP-7 and the activation of transcription factors such as NF-κB and AP-1. MMP-7 upregulation was not affected by NF-κB, but it was related to AP-1 activation. In BFT-exposed IECs, syndecan-2 release was observed in a time- and concentration-dependent manner. MMP-7 suppression was associated with a reduction in syndecan-2 release. In addition, suppression of ERK, one of the mitogen-activated protein kinases (MAPKs), inhibited AP-1 activity and MMP-7 expression. Furthermore, the suppression of AP-1 and ERK activity was related to the attenuation of syndecan-2 release. These results suggest that a signaling cascade comprising ERK and AP-1 activation in IECs is involved in MMP-7 upregulation and syndecan-2 release during exposure to BFT.

Mitogen-activated protein kinases mediate peroxynitrite-induced cell death in human bronchial epithelial cells

2003 ◽  
Vol 284 (6) ◽  
pp. L1112-L1120 ◽  
Author(s):  
Elodie Nabeyrat ◽  
Gina E. Jones ◽  
Peter S. Fenwick ◽  
Peter J. Barnes ◽  
Louise E. Donnelly
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Protein Kinases ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Bronchial Epithelial ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein ◽  
Sb 239063

Peroxynitrite, formed by the reaction of nitric oxide (NO · ) with superoxide anions (O[Formula: see text]·), may play a role in the pathophysiology of inflammation. The effects of 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, on the human bronchial epithelial cell line BEAS-2B, were examined. SIN-1 exposure resulted in cell death in a time- and dose-dependent manner. Depletion of intracellular glutathione increased the vulnerability of the cells. Pretreatment with Mn(III)tetrakis( N-methyl-4′-pyridyl)porphyrin (MnTMPyP) or hydroxocobalamin (HC), O[Formula: see text]· and NO · scavengers, respectively, reduced significantly SIN-1-induced cell death (18.66 ± 3.57 vs. 77.01 ± 14.07 or 82.20 ± 9.64, % cell viability SIN-1 vs. MnTMPyP or HC). Moreover, the mitogen-activated protein kinases (MAPK) p44/42 (ERK), p38, and p54/46 (JNK) were also activated in a time- and concentration-dependent manner. PD-98059 and SB-239063, specific inhibitors of ERK and p38 MAPK pathways, failed to protect cells against 1 mM SIN-1. However, PD-98059 partially inhibited (60% cell survival) SIN-1 effects at ≤0.25 mM, and this was increased with the inclusion of SB-239063. Therefore, MAPKs may mediate signal transduction pathways induced by peroxynitrite in lung epithelial cells leading to cell death.

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