Search

Your search keyword '"GIOVINO, CONCETTA"' showing total 2 results
Start Over Author "GIOVINO, CONCETTA" Topic nf-kappa b
2 results on '"GIOVINO, CONCETTA"'

1. PEI-engineered respirable particles delivering a decoy oligonucleotide to NF-κB: inhibiting MUC2 expression in LPS-stimulated airway epithelial cells.

Author

Ungaro F, De Stefano D, Giovino C, Masuccio A, Miro A, Sorrentino R, Carnuccio R, and Quaglia F

Subjects
Bronchi cytology, Bronchi metabolism, Cells, Cultured, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Cells metabolism, Humans, Interleukin-8 genetics, Microscopy, Electron, Scanning, NF-kappa B metabolism, Oligonucleotides chemistry, Bronchi drug effects, Lipopolysaccharides pharmacology, Mucin-2 antagonists & inhibitors, NF-kappa B genetics, Oligonucleotides administration & dosage, Polyethyleneimine chemistry
Abstract

A specific and promising approach to limit inflammation and mucin iperproduction in chronic lung diseases relies on specific inhibition of nuclear Factor-κB (NF-κB) by a decoy oligonucleotide (dec-ODN). To fulfill the requirements dictated by translation of dec-ODN therapy in humans, inhalable dry powders were designed on a rational basis to provide drug protection, sustained release and to optimize pharmacological response. To this end, large porous particles (LPP) for dec-ODN delivery made of a sustained release biomaterial (poly(lactic-co-glycolic) acid, PLGA) and an "adjuvant" hydrophilic polymer (polyethylenimine, PEI) were developed and their effects on LPS-stimulated human airway epithelial cells evaluated. The composite PLGA/PEI particles containing dec-ODN (i.e., LPP(PEI)) were successfully engineered for widespread deposition in the lung and prolonged release of intact dec-ODN in vitro. LPP(PEI) caused a prolonged inhibition of IL-8 and MUC2 expression in CF human bronchial epithelial cells and human epithelial pulmonary NCI-H292 cells, respectively, as compared to naked dec-ODN. Nonetheless, as compared to previously developed LPP, the presence of PEI was essential to construct a dec-ODN delivery system able to act in mucoepidermoid lung epithelial cells. In perspective, engineering LPP with PEI may become a key factor for tuning carrier properties, controlling lung inflammation and mucin production which, in turn, can foster in vivo translation of dec-ODN therapy.

Published
2012
Full Text
View/download PDF

2. Sustained inhibition of IL-6 and IL-8 expression by decoy ODN to NF-κB delivered through respirable large porous particles in LPS-stimulated cystic fibrosis bronchial cells

Author

Francesca Ungaro, A. Polimeno, Rosa Carnuccio, Daniela De Stefano, Fabiana Quaglia, Concetta Giovino, DE STEFANO, Daniela, Ungaro, Francesca, Giovino, Concetta, Polimeno, A., Quaglia, Fabiana, and Carnuccio, Rosa

Subjects
oligonucleotide, Lipopolysaccharides, Lipopolysaccharide, Cystic Fibrosis, pulmonary delivery, Inflammation, Bronchi, Electrophoretic Mobility Shift Assay, Biology, Cystic fibrosis, chemistry.chemical_compound, Drug Discovery, Genetics, medicine, Humans, Interleukin 8, Interleukin 6, Molecular Biology, Genetics (clinical), Cells, Cultured, DNA Primers, Analysis of Variance, dry powders, Interleukin-6, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-8, NF-kappa B, Interleukin, hemic and immune systems, NF-κB, respiratory system, medicine.disease, Molecular biology, Cystic fibrosis transmembrane conductance regulator, chemistry, Gene Expression Regulation, Oligodeoxyribonucleotides, Immunology, Pseudomonas aeruginosa, biology.protein, Molecular Medicine, medicine.symptom, Transcription Factors
Abstract

Background Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Neutrophil-dominated inflammation and chronic bacterial infection are still considered the primary cause of bronchioectasis, respiratory failure and consequent death in CF patients. Activation of nuclear factor (NF)-κB is responsible for overproduction of cytokines, such as interleukin (IL)-6 and IL-8, in airways of CF patients. Thus, decoy oligodeoxynucleotides against NF-κB (dec-ODN) may limit lung inflammation in CF. In the present study, we studied the effects of dec-ODN delivered through biodegradable and respirable poly(D,L-lactide-co-glycolide) large porous particles (LPP) on IL-6 and IL-8 mRNA expression as well as NF-κB/DNA binding activity in cystic fibrosis cells stimulated with lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Methods dec-ODN LPP were prepared by a modified double emulsion technique and characterized in terms of size, morphology, tapped density and dec-ODN loading. Human epithelial bronchial IB3-1 (CFTR-mutated) as well as S9 (CFTR-corrected) were stimulated with LPS from P. aeruginosa for 24 and 72 h in the absence or presence of naked dec-ODN or dec-ODN LPP. Results Stimulation of cells with LPS from P. aeruginosa caused an increase of IL-6 and IL-8 mRNA levels, which were significantly inhibited by dec-ODN LPP at 24 and 72 h, whereas naked dec-ODN inhibited those only at 24 h. Similar effects were exhibited by dec-ODN LPP or naked dec-ODN on NF-κB/DNA binding activity. Conclusions Our observations indicate that respirable biodegradable dec-ODN LPP may represent a promising strategy for inhibiting NF-κB transcriptional activity and related gene expression and, thus, reduce lung chronic inflammation in CF patients. Copyright © 2011 John Wiley & Sons, Ltd.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results