USP14-mediated IκBα degradation exacerbates NF-κB activation and IL-1β-stimulated chondrocyte dedifferentiation

Life Sciences ◽  
2019 ◽  
Vol 218 ◽  
pp. 147-152 ◽  
Author(s):  
Ming Li ◽  
Jianqiang Zhao ◽  
Liang Jia
Keyword(s):  
Iκbα Degradation

EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption

2001 ◽  
Vol 281 (4) ◽  
pp. G890-G898 ◽  
Author(s):  
Suzana D. Savkovic ◽  
Akila Ramaswamy ◽  
Athanasia Koutsouris ◽  
Gail Hecht
Keyword(s):  
Tight Junction ◽  
Signaling Cascades ◽  
Extracellular Signal Regulated Kinase ◽  
Intestinal Epithelia ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Functional Consequences ◽  
First Time ◽  
Necrosis Factor ◽  
Iκbα Degradation

Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation of nuclear factor (NF)-κB, and paracellular permeability is enhanced via a Ca2+- and myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study were to identify signaling pathways by which EPEC triggers inflammation and to determine whether these pathways parallel or diverge from those that alter permeability. EPEC-induced phosphorylation and degradation of the primary inhibitor of NF-κB (IκBα) were tumor necrosis factor (TNF)-α and interleukin (IL)-1β independent. In contrast to Salmonella typhimurium, EPEC-stimulated IκBα degradation and IL-8 expression did not require Ca2+. Instead, extracellular signal-regulated kinase (ERK)-1/2 was significantly and rapidly activated. ERK1/2 inhibitors attenuated IκBα degradation and IL-8 expression. Although ERK1/2 can activate MLCK, its inhibition had no impact on EPEC disruption of the tight junction barrier. In conclusion, EPEC-induced inflammation 1) is TNF-α and IL-1β receptor independent, 2) utilizes pathways differently from S. typhimurium, 3) requires ERK1/2, and 4) employs signals that are distinct from those that alter permeability. This is the first time that EPEC-activated signaling cascades have been linked to independent functional consequences.

Proteasome Inhibitors Induce Inhibitory κB (IκB) Kinase Activation, IκBα Degradation, and Nuclear Factor κB Activation in HT-29 Cells

2004 ◽  
Vol 65 (2) ◽  
pp. 342-349 ◽  
Author(s):  
Zoltán H. Németh ◽  
Hector R. Wong ◽  
Kelli Odoms ◽  
Edwin A. Deitch ◽  
Csaba Szabó ◽  
...  
Keyword(s):  
Proteasome Inhibitors ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Kinase Activation ◽  
Iκb Kinase ◽  
Ht 29 ◽  
Iκbα Degradation

Caerulein-induced NF-κB/Rel activation requires both Ca2+ and protein kinase C as messengers

1999 ◽  
Vol 277 (3) ◽  
pp. G678-G686 ◽  
Author(s):  
Yusuke Tando ◽  
Hana Algül ◽  
Martin Wagner ◽  
Hans Weidenbach ◽  
Guido Adler ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Atpase Inhibitor ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Intracellular Ca ◽  
Iκbα Degradation

The eukaryotic transcription factor NF-κB/Rel is activated by a large variety of stimuli. We have recently shown that NF-κB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-κB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-κB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IκBα. IκBβ was only slightly affected by caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-κB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IκBα degradation and subsequent nuclear translocation of NF-κB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-κB/Rel activation and IκBα degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-κB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-κB/Rel activation.

Pentoxifylline downregulates α (I) collagen expression by the inhibition of Iκbα degradation in liver stellate cells

2007 ◽  
Vol 24 (4) ◽  
pp. 303-314 ◽  
Author(s):  
E. Hernández ◽  
L. Bucio ◽  
V. Souza ◽  
M. C. Escobar ◽  
L. E. Gómez-Quiroz ◽  
...  
Keyword(s):  
Stellate Cells ◽  
Collagen Expression ◽  
Iκbα Degradation

scholarly journals Mediation by NF-κB of cytokine induced expression of intercellular adhesion molecule 1 (ICAM-1) in an intestinal epithelial cell line, a process blocked by proteasome inhibitors

Gut ◽  
1998 ◽  
Vol 42 (6) ◽  
pp. 779-787 ◽  
Author(s):  
C Jobin ◽  
C Hellerbrand ◽  
L L Licato ◽  
D A Brenner ◽  
R B Sartor
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Nuclear Translocation ◽  
Proteasome Inhibitors ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Iκbα Degradation

Background/aims—The gene promoter for the intercellular adhesion molecule ICAM-1 possesses binding sites for several transcriptional factors, including nuclear factor κB (NF-κB). The role of NF-κB in ICAM-1 gene regulation was therefore examined by using different proteasome inhibitors in tumour necrosis factor α (TNF-α) stimulated IEC-6 rat intestinal epithelial cells.Methods—ICAM-1 expression was analysed by enzyme linked immunosorbent assay (ELISA), reverse transcriptase polymerase chain reaction, and immunohistochemistry. Steady state levels of cytoplasmic IκB protein were evaluated by western blot, and nuclear translocation of NF-κB was determined by electrophoretic mobility shift assay and immunofluorescence staining. Cell adhesion was assayed by measuring the binding of fluorescence labelled MOLT-4 cells.Results—TNF-α induced ICAM-1 mRNA and protein expression in IEC-6 cells, which was followed by increased adhesion of MOLT-4 lymphocytes. Blocking TNF-α induced IκBα degradation with proteasome inhibitors reduced TNF-α induced NF-κB activation and ICAM-1 gene induction and notably decreased MOLT-4 cell adhesion without affecting Jun N-terminal kinase (JNK/SAPK) activity or de novo protein synthesis.Conclusion—TNF-α induction of ICAM-1 expression is mediated by the transcription factor NF-κB and can be inhibited by blocking IκBα degradation. Thus the IκB/NF-κB system is a promising target for pharmacological modulation of the expression of adhesion molecules and other inflammatory genes in the intestine.

scholarly journals San-Huang-Xie-Xin-Tang Protects against Activated Microglia- and 6-OHDA-Induced Toxicity in Neuronal SH-SY5Y Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Yu-Tzu Shih ◽  
Ing-Jun Chen ◽  
Yang-Chang Wu ◽  
Yi-Ching Lo
Keyword(s):  
Cell Viability ◽  
Nuclear Translocation ◽  
Peptic Ulcers ◽  
Gastric Bleeding ◽  
Neuroprotective Effects ◽  
Mitochondria Membrane Potential ◽  
Traditional Chinese Herbal Medicine ◽  
Activated Microglia ◽  
Cox 2 ◽  
Iκbα Degradation

San-Huang-Xie-Xin-Tang (SHXT), composed ofCoptidis rhizoma,Scutellariae radixandRhei rhizoma, is a traditional Chinese herbal medicine used to treat gastritis, gastric bleeding and peptic ulcers. This study investigated the neuroprotective effects of SHXT on microglia-mediated neurotoxicity using co-cultured lipopolysaccharide (LPS)-activated microglia-like BV-2 cells with neuroblastoma SH-SY5Y cells. Effects of SHXT on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were also examined in SH-SY5Y cells. Results indicated SHXT inhibited LPS-induced inflammation of BV-2 cells by downregulation of iNOS, NO, COX-2, PGE2, gp91phox, iROS, TNF-α, IL-1β, inhibition of IκBα degradation and upregulation of HO-1. In addition, SHXT increased cell viability and down regulated nNOS, COX-2 and gp91phoxof SH-SY5Y cells co-cultured with LPS activated BV-2 cells. SHXT treatment increased cell viability and mitochondria membrane potential (MMP), decreased expression of nNOS, COX-2, gp91phoxand iROS, and inhibited IκBα degradation in 6-OHDA-treated SH-SY5Y cells. SHXT also attenuated LPS activated BV-2 cells- and 6-OHDA-induced cell death in differentiated SH-SY5Y cells with db-cAMP. Furthermore, SHXT-inhibited nuclear translocation of p65 subunit of NF-κB in LPS treated BV-2 cells and 6-OHDA treated SH-SY5Y cells. In conclusion, SHXT showed protection from activated microglia- and 6-OHDA-induced neurotoxicity by attenuating inflammation and oxidative stress.

Calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance in colorectal cancer xenografts

2012 ◽  
Vol 227 (1) ◽  
pp. 118-129 ◽  
Author(s):  
Nina Fenouille ◽  
Sebastien Grosso ◽  
SU Yunchao ◽  
Didier Mary ◽  
Rodolphe Pontier-Bres ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Secondary Resistance ◽  
Calpain 2 ◽  
Iκbα Degradation
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