Almeida Marcos Paulo Oliveira, Mota Caroline Martins, Mineo Tiago Wilson Patriarca, Ferro Eloisa Amália Vieira, Barbosa Bellisa Freitas, Silva Neide Maria
Laboratory of Immunopathology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil.
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo," Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil.
Front Microbiol. 2021 Apr 12;12:659028. doi: 10.3389/fmicb.2021.659028. eCollection 2021.
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 . It was previously shown that HO-1 activity was involved in the control of infection ; however, its contribution in trophoblast cells during infection, remain undefined. Thus, this study aimed to investigate the influence of HO-1 in -infected BeWo and HTR-8/SVneo human trophoblast cells. For this purpose, trophoblast cells were infected and the HO-1 expression was evaluated. -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 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. 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 -infected cells, which was associated with the control of infection.
血红素加氧酶-1(HO-1)在母胎界面发挥有益作用,尤其是在滋养层细胞中,参与这些细胞表型的存活和成熟。滋养层细胞在整个孕期发挥着至关重要的作用,是病原体垂直传播的通道,例如 。先前的研究表明,HO-1活性参与了 感染的控制;然而,其在 感染期间对滋养层细胞的贡献仍不明确。因此,本研究旨在探讨HO-1对感染 的BeWo和HTR-8/SVneo人滋养层细胞的影响。为此,对滋养层细胞进行感染并评估HO-1的表达。感染 的BeWo细胞用HO-1的诱导剂血红素或氯化钴卟啉处理,或用HO-1的终产物胆红素处理,并对寄生虫感染情况进行定量分析。同时还评估了HO-1的调节因子p38丝裂原活化蛋白激酶(p38 MAPK)的参与情况以及细胞因子的产生。结果发现, 在BeWo细胞中降低了HO-1的表达,但在HTR-8/SVneo细胞中没有。当用HO-1诱导剂或胆红素处理时,BeWo细胞减少了寄生虫的增殖。 在BeWo细胞中也降低了p38 MAPK的磷酸化;另一方面,HO-1的诱导维持了其激活。最后,在感染 的细胞中,HO-1的诱导上调了白细胞介素-6(IL-6)的产生,这与感染的控制有关。