TY - JOUR
T1 - Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages
AU - Aguayo-Cerón, Karla A.
AU - Gutiérrez-Iglesias, Gisela
AU - Parra-Barrera, Alberto
AU - Ocharan-Hernández, María E.
AU - Romero-Nava, Rodrigo
AU - Jiménez-Zamarripa, Carlos A.
AU - Calzada-Mendoza, Claudia C.
N1 - Publisher Copyright:
© 2020
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Foam cells
KW - Inflammation
KW - Macrophage
KW - Tibolone
UR - http://www.scopus.com/inward/record.url?scp=85098981870&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2020.108779
DO - 10.1016/j.steroids.2020.108779
M3 - Artículo
C2 - 33383063
AN - SCOPUS:85098981870
SN - 0039-128X
VL - 167
JO - Steroids
JF - Steroids
M1 - 108779
ER -