Inhibition of NF-κB by ACT001 reduces fibroblast activity in idiopathic pulmonary fibrosis.
Biomed Pharmacother
; 138: 111471, 2021 Jun.
Article
en En
| MEDLINE
| ID: mdl-33730605
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and poor prognosis. In IPF, aberrant extracellular matrix production by activated, hyperproliferative fibroblasts drives disease progression but the exact mechanisms by which this occurs remains undefined. The transcription factor nuclear factor kappa-B (NF-ĸB) has been suggested as a potential therapeutic target in IPF and therefore the aim of this study was to investigate the efficacy of ACT001, an NF-ĸB inhibitor, on primary fibroblasts derived from patients with and without IPF. Primary lung fibroblasts derived from eight patients with IPF and eight age-matched non-diseased controls (NDC) were treated with 0-10 µM ACT001 and the effects on fibroblast activity (viability and proliferation, fibroblast-to-myofibroblast transition, fibronectin expression), interleukin (IL)-6 and IL-8 cytokine release were quantified. ACT001 inhibited fibroblast activity in a concentration-dependent manner in both groups of fibroblasts. ACT001 inhibited IL-6 but not IL-8 production in unstimulated fibroblasts. ACT001 is a water-soluble compound with a stable half-life in plasma, thus making it an attractive candidate for further investigation as a therapeutic in IPF. This study adds to the growing body of literature that demonstrates anti-fibrotic activity of NF-ĸB inhibition in the context of IPF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
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FN-kappa B
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Fibrosis Pulmonar Idiopática
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Fibroblastos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Francia