Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.
Foam cells
Inflammation
Macrophage
Tibolone
Journal
Steroids
ISSN: 1878-5867
Titre abrégé: Steroids
Pays: United States
ID NLM: 0404536
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
13
09
2020
revised:
07
12
2020
accepted:
18
12
2020
pubmed:
1
1
2021
medline:
25
11
2021
entrez:
31
12
2020
Statut:
ppublish
Résumé
Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1β, IL-6, TNF-α, NOS2, ARG1, TGFβ) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1β, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.
Sections du résumé
BACKGROUND
Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures.
METHODS
To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1β, IL-6, TNF-α, NOS2, ARG1, TGFβ) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA.
RESULTS
It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1β, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm.
CONCLUSIONS
These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.
Identifiants
pubmed: 33383063
pii: S0039-128X(20)30205-1
doi: 10.1016/j.steroids.2020.108779
pii:
doi:
Substances chimiques
Cytokines
0
Lipoproteins, LDL
0
Reactive Oxygen Species
0
oxidized low density lipoprotein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108779Informations de copyright
Copyright © 2020. Published by Elsevier Inc.