4'OMethylalpinumisoflavone inhibits the activation of monocytes/macrophages to an immunostimulatory phenotype induced by 27hydroxycholesterol.
Int J Mol Med
; 43(5): 2177-2186, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-30896858
ABSTRACT
The epidemiological, animal and cell effects of plant metabolites suggest versatile health benefits of flavonoids. However, whether flavonoids affect the deleterious biological activity of oxygenated cholesterol molecules remains to be elucidated. The present study investigated the effects of 4'Omethylalpinumisoflavone (mAI) isolated from Maclura tricuspidata (Cudrania tricuspidata) on the 27hydroxycholesterol (27OHChol)induced activation of monocytes/macrophages using human THP1 cells. mAI dosedependently impaired the expression of CC motif chemokine ligand (CCL)2 chemokine and the migration of monocytic cells enhanced by 27OHChol. mAI downregulated the surface and cellular levels of CD14 and inhibited the release of soluble CD14. This isoflavone significantly weakened the lipopolysaccharide responses that were enhanced in the presence of 27OHChol, and inhibited the transcription and secretion of the active gene product of matrix metalloproteinase9. mAI also suppressed the expression of CC motif chemokine receptor 5 ligands, including CL3 and CCL4, and M1phenotype markers induced by 27OHChol. Furthermore, mAI impaired phosphorylation of the nuclear factorκB p65 subunit without affecting the phosphorylation of Akt. These results indicate that mAI inhibits the activation of monocytes/macrophages to the immunostimulatory phenotype in a milieu rich in 27OHChol, suggesting potential benefits of the flavonoid for the treatment of diseases in which the pathogenesis is linked to 27OHCholinduced inflammatory responses.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hidroxicolesteroles
/
Isoflavonas
/
Activación de Macrófagos
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article