Exploring the anti-inflammatory and anti-fibrotic activity of NFκB decoy oligodeoxynucleotide-loaded spermine-functionalized acetalated nanoparticles.
Chem Biol Interact
; 396: 111059, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38761875
ABSTRACT
Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli like lipopolysaccharide (LPS) activate macrophages and dendritic cells, with concomitant M1 polarization and release of pro-inflammatory cytokines. Chronic inflammation and oxidative stress lead to airway remodelling causing irreversible functional and structural alterations of the lungs. Airway remodelling is multifactorial, however, the hormone transforming growth factor-ß (TGF-ß) is one of the main contributors to fibrotic changes. The signalling pathways mediating inflammation and remodelling rely both on the transcription factor nuclear factor-κB (NFκB), underlying the potential of NFκB inhibition as a therapeutic strategy for chronic respiratory disorders. In this study, we encapsulated an NFκB-inhibiting decoy oligodeoxynucleotide (ODN) in spermine-functionalized acetalated dextran (SpAcDex) nanoparticles and tested the in vitro anti-inflammatory and anti-remodelling activity of this formulation. We show that NF-κB ODN nanoparticles counteract inflammation by reversing LPS-induced expression of the activation marker CD40 in myeloid cells and counteracts remodelling features by reversing the TGF-ß-induced expression of collagen I and α-smooth muscle actin in human dermal fibroblast. In summary, our study highlights the great potential of inhibiting NFκB via decoy ODN as a therapeutic strategy tackling multiple pathophysiological features underlying chronic respiratory conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligodesoxirribonucleótidos
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Espermina
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Lipopolisacáridos
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FN-kappa B
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Nanopartículas
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Antiinflamatorios
Límite:
Humans
Idioma:
En
Revista:
Chem Biol Interact
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia