Reference : Role of IKK and ERK pathways in intrinsic inflammation of cystic fibrosis airways
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Pharmacy, pharmacology & toxicology
Role of IKK and ERK pathways in intrinsic inflammation of cystic fibrosis airways
Verhaeghe, Catherine [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine >]
Remouchamps, Caroline mailto [Université de Liège - ULiège > > Virologie - Immunologie >]
Hennuy, Benoît mailto [Université de Liège - ULiège > > GIGA-Management : Plate-forme transcriptomique >]
Vanderplasschen, Alain mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Chariot, Alain mailto [Université de Liège - ULiège > Département de pharmacie > Chimie médicale >]
Tabruyn, Sébastien P [> > > >]
Oury, Cécile mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Bours, Vincent mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Biochemical Pharmacology
Elsevier Science
Yes (verified by ORBi)
United Kingdom
[en] NF-kappa B ; AP-1 ; transcription factors ; inflammation ; CFTR ; gene expression ; Mutation ; Transcription Factor AP-1/metabolism ; Trachea/cytology/embryology ; Reverse Transcriptase Polymerase Chain Reaction ; NF-kappa B/metabolism ; Interleukin-8/metabolism ; Models, Biological ; Luciferases/metabolism ; Cell Line, Transformed ; Interleukin-6/metabolism ; Gene Expression ; Inflammation/pathology ; Interleukin-1beta/metabolism ; I-kappa B Kinase/antagonists & inhibitors/metabolism ; Homozygote ; Humans ; Genes, Reporter ; Hela Cells ; Fibroblast Growth Factor 2/metabolism ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism ; Enzyme-Linked Immunosorbent Assay ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Chemokine CXCL1 ; Chemokine CXCL2 ; Chemokines, CXC/metabolism ; Cystic Fibrosis/metabolism/pathology
[en] in cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality and may precede bacterial colonization. The aim of the present study was to investigate the molecular mechanisms underlying intrinsic inflammation in cystic fibrosis air-ways. Using different cystic fibrosis cell models, we first demonstrated that, beside a high constitutive nuclear factor of kappaB (NF-kappa B) activity, CF cells showed a higher activator protein-1 (AP-1) activity as compared to their respective control cells. Gene expression profiles, confirmed by RT-PCR and ELISA, showed over-expression of numerous NF-KB and AP-1-dependent pro-inflammatory genes in CF cells in comparison with control cells. Activation of NF-KB was correlated with higher inhibitor of kappa B kinase (IKK) activity. In addition, Bio-plex phosphoprotein assays revealed higher extracellular signal-regulated kinase (ERK) phosphorylation in CFT-2 cells. Inhibition of this kinase strongly decreased expression of pro-inflammatory genes coding for growth-regulated proteins (Gro-alpha, Gro-beta and Gro-gamma) and interleukins (IL-1 beta, IL-6 and IL-8). Moreover, inhibition of secreted interleukin-1 beta (IL-1 beta) and basic fibroblast growth factor (bFGF) with neutralizing antibodies reduced pro-inflammatory gene expression. Our data thus demonstrated for the first time that the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) at the plasma membrane leads to an intrinsic AP-1, in addition to NF-kappa B, activity and consequently to a pro-inflammatory state sustained through autocrine factors such as IL-1 beta and bFGF. (c) 2007 Elsevier Inc. All rights reserved.
Giga-Signal Transduction
Researchers ; Professionals ; Students

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