Abstract
Heme oxygenase-1 (HO-1) enzyme exerts beneficial effects at the maternal-fetal interface, especially in trophoblasts, being involved in survival and maturation of these cell phenotypes. Trophoblast cells play essential roles throughout pregnancy, being the gateway for pathogens vertically transmitted, such as Toxoplasma gondii. It was previously shown that HO-1 activity was involved in the control of T. gondii infection in vivo; however, its contribution in trophoblast cells during T. gondii infection, remain undefined. Thus, this study aimed to investigate the influence of HO-1 in T. gondii-infected BeWo and HTR-8/SVneo human trophoblast cells. For this purpose, trophoblast cells were infected and the HO-1 expression was evaluated. T. gondii-infected BeWo cells were treated with hemin or CoPPIX, as inducers of HO-1, or with bilirubin, an end-product of HO-1, and the parasitism was quantified. The involvement of p38 MAPK, a regulator of HO-1, and the cytokine production, were also evaluated. It was found that T. gondii decreased the HO-1 expression in BeWo but not in HTR-8/SVneo cells. When treated with the HO-1 inducers or bilirubin, BeWo cells reduced the parasite proliferation. T. gondii also decreased the p38 MAPK phosphorylation in BeWo cells; on the other hand, HO-1 induction sustained its activation. Finally, the IL-6 production was upregulated by HO-1 induction in T. gondii-infected cells, which was associated with the control of infection.
Highlights
The placenta is a transient organ formed during human pregnancy, responsible for establishing an important maternalfetal communication which performs metabolic, nutritional, endocrine, and immunological functions, favoring a successful embryonic development
Our data obtained from western blotting assays revealed that HO1 expression was significantly reduced in T. gondii-infected BeWo cells in comparison with the control non-infected cells (P = 0.0226), as observed in the representative protein bands (Figure 1A) and densitometric analysis (Figure 1B)
In the absence of T. gondii, the Heme oxygenase-1 (HO-1) expression in normal conditions was significantly higher in BeWo cells than in HTR-8/SVneo (P = 0.0286), suggesting that BeWo villous trophoblast cells present more amounts of heme oxygenase (HO)-1 than HTR-8/SVneo extravillous trophoblasts
Summary
The placenta is a transient organ formed during human pregnancy, responsible for establishing an important maternalfetal communication which performs metabolic, nutritional, endocrine, and immunological functions, favoring a successful embryonic development (reviewed by Burton and Fowden, 2015). The normal placentation occurs by the direct contact of trophoblast cells with the maternal decidua, which comprises the developed endometrium, constituted by endometrial glands, uterine blood vessels, decidual stromal cells, and immune cells. The interaction between these fetal and maternal elements constitutes the maternalfetal interface (reviewed by Knöfler et al, 2019; Turco and Moffett, 2019). Highly proliferative and fusogenic cells that originate an additional cell component, the syncytiotrophoblast Together, these constitute the chorionic villi, structures that anchor to the decidua. One of the key cellular elements that contribute with the maternal-fetal tolerance and placental physiology is the heme oxygenase (HO) enzymatic system (reviewed by Levytska et al, 2013)
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