Activated THP-1 Macrophage-Derived Factors Increase the Cytokine, Fractalkine, and
EGF Secretions, the Invasion-Related MMP Production, and Antioxidant Activity of HEC-1A
Endometrium Cells
(Recovery and Resilience Facility of the European Union within the framework of Programme
Széchenyi Plan Plus)
(RRF-2.3.1-21-2022-00012)
Endometrium receptivity is a multifactor-regulated process involving progesterone
receptor-regulated signaling, cytokines and chemokines, and additional growth regulatory
factors. In the female reproductive system, macrophages have distinct roles in the
regulation of receptivity, embryo implantation, immune tolerance, and angiogenesis
or oxidative stress. In the present study, we investigated the effects of PMA-activated
THP-1 macrophages on the receptivity-related genes, cytokines and chemokines, growth
regulators, and oxidative stress-related molecules of HEC-1A endometrium cells. We
established a non-contact co-culture in which the culture medium of the PMA-activated
macrophages exhibiting the pro-inflammatory phenotype was used for the treatment of
the endometrial cells. In the endometrium cells, the expression of the growth-related
factors activin and bone morphogenetic protein 2, the growth hormone EGF, and the
activation of the downstream signaling molecules pERK1/2 and pAkt were analyzed by
ELISA and Western blot. The secretions of cytokines and chemokines, which are involved
in the establishment of endometrial receptivity, and the expression of matrix metalloproteinases
implicated in invasion were also determined. Based on the results, the PMA-activated
THP-1 macrophages exhibiting a pro-inflammatory phenotype may play a role in the regulation
of HEC-1A endometrium cells. They alter the secretion of cytokines and chemokines,
as well as the protein level of MMPs of HEC-1A cells. Moreover, activated THP-1 macrophages
may elevate oxidative stress protection of HEC-1A endometrium cells. All these suggest
that pro-inflammatory macrophages have a special role in the regulation of receptivity-related
and implantation-related factors of HEC-1A cells.