Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production

Barbosa, Bellisa Freitas; Paulesu, Luana; Ietta, Francesca; Bechi, Nicoletta; Romagnoli, Roberta; Gomes, A. da S.; Favoreto-Junior, S.; Silva, D.A.O.; Mineo, José Roberto; Ferro, Eloísa Amália Vieira

doi:10.1016/j.placenta.2013.12.013

Cited by 44 publications

(90 citation statements)

References 45 publications

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“…The BeWo cells were obtained from the American Type Culture Collection (Manassas, VA) and maintained in 75-cm 2 culture flasks in Roswell Park Memorial Institute (RPMI) 1640 medium (Cultilab, Campinas, SP, Brazil) supplemented with 100 units/ml penicillin, 100 lg/ml streptomycin (Sigma Chemical Co., St. Louis, MO), and 10% heat-inactivated fetal bovine serum (FBS) (Cultilab) in a humidified incubator at 378C and 5% CO 2 [19].…”

Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

“…The parasites were propagated in BeWo cells maintained in RPMI 1640 medium supplemented with penicillin, streptomycin, and 2% FBS at 378C and 5% CO 2 [19].…”

Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

“…Uninfected and untreated cells were used as controls and maintained in RPMI 1640 medium with 2% FBS. Next, cells were harvested, centrifuged at 400 3 g for 5 min and lysed on ice with lysis buffer (50 mM TrisHCl, pH 8.0, 0.1 mM ethylenediaminetetraacetic acid, 0.5% Triton X-100, 10% glycerol, 1 mM dithiothreitol, and 200 mM NaCl) supplemented with a protease inhibitor cocktail (Complete; Roche Diagnostic, Mannheim, Germany), 1 mM sodium orthovanadate (Na 3 VO 4 ) and sodium fluoride (NaF) (both from Sigma) and submitted to three freeze-thaw cycles [19]. After centrifugation at 15 000 3 g for 15 min at 48C, the supernatants were collected, the concentration of total protein was measured using the Bradford assay [39], and the samples were submitted to Western blot analysis.…”

Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

“…On the other hand, a normal pregnancy is characterized by a preferential Th2-type immune response and T regulatory cell responses [11], with the production of anti-inflammatory cytokines such as interleukin 10 (IL10) and transforming growth factor beta1 (TGFB1) by both maternal and fetal cells, including trophoblast cells [12,13]. The role of trophoblast cells in the immunology of pregnancy, especially in the presence of intracellular pathogens such as T. gondii and Neospora caninum, has been studied by our group using wellestablished cell lines, such as BeWo cells [14][15][16][17][18][19]. These cells were isolated from a human choriocarcinoma [20] and preserved their trophoblastic characteristics, such as hormone production and cytokine release under in vitro stimulation [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Even though BeWo cells are derived from a choriocarcinoma, they are becoming an excellent in vitro model to investigate T. gondii infection in trophoblast cells. In fact, our group has investigated several aspects of the immunology of pregnancy using these cells as a trophoblast model, including their cross-talk with monocytes [18] and the role of cytokines and drugs during T. gondii infection [14,15,17,19].…”

Section: Introductionmentioning

confidence: 99%

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IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Barbosa

Lopes-Maria

Gomes

et al. 2015

Biology of Reproduction

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Considering that interleukin 10 (IL10), transforming growth factor beta1 (TGFB1), and interferon gamma (IFNG) are involved in the susceptibility of BeWo trophoblast cells to Toxoplasma gondii infection, the aim of the present study was to investigate the effector mechanisms triggered by these cytokines in the control of T. gondii in BeWo cells. For this purpose, infected/uninfected BeWo cells were treated with IL10, TGFB1 (50 ng/ml), and IFNG (20 or 100 ng/ml) in order to verify the phosphorylation of signal transducers and activators of transcription 1 (STAT1), STAT3, and Smad2, parasite intracellular proliferation, as well as the Th1/Th2/IL17A cytokine production. The treatment of BeWo cells with IL10 and TGFB1 favored T. gondii proliferation, and these findings were associated with STAT3 and Smad2 phosphorylation, respectively (P < 0.05). Also, these cytokine treatments were able to down-modulate TNF alpha (TNFA) and IL6 production (P < 0.05). Low concentration of IFNG was unable to control T. gondii infection but was able to trigger STAT1 phosphorylation and up-regulate IL6 and IL17A production; whereas a high concentration of IFNG was unable to activate STAT1 but down-modulated IL6 and TNFA and increased T. gondii proliferation (P < 0.05). IL10, TGFB1, and IFNG regulate a differential T. gondii proliferation in BeWo cells because they distinctly trigger intracellular signaling pathways and cytokine production, especially IL6 and TNFA. Our data open new windows to understand the mechanisms triggered by IL10, TGFB1, and IFNG at the maternal-fetal interface in the presence of T. gondii, contributing to recognizing the importance of these effector mechanisms involved in the vertical transmission of this parasite.

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Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

“…The parasites were propagated in BeWo cells maintained in RPMI 1640 medium supplemented with penicillin, streptomycin, and 2% FBS at 378C and 5% CO 2 [19].…”

Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

Section: Ethics Statement Cell Culture and Parasitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Barbosa

Lopes-Maria

Gomes

et al. 2015

Biology of Reproduction

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Macrophage migration inhibitory factor (MIF) promotes rat airway muscle cell proliferation and migration mediated by ERK1/2 and FAK signaling

Lan

Wang

Chen

et al. 2017

Cell Biology International

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Macrophage migration inhibitory factor (MIF) is an inflammatory mediator that contributes to asthmatic airway remodeling; however, little is known regarding the effects of MIF on airway smooth muscle cells (ASMCs). In the present study, we found that an enhanced expression of MIF promoted ASMC proliferation, increased the population of cells in the S/G2 phase, downregulated P21 expression, and upregulated cyclin D1, cyclin D3, and Cdk6 expression. In addition, the apoptosis of ASMCs was significantly decreased in response to MIF overexpression, compared with the negative control. Moreover, MIF facilitated the migration of ASMCs by upregulating the expression of matrix metalloproteinase (MMP)-2. Finally, we showed that MIF increased the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and focal adhesion kinase (FAK), which are associated with proliferation and migration. In conclusion, this study demonstrated that MIF overexpression promotes the proliferation and migration of ASMCs by upregulating the activity of the ERK1/2 and FAK signaling pathways in these cells, further indicating that inhibition of MIF may prove to be an effective strategy for treating asthma patients with airway remodeling.

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Experimental models of maternal–fetal interface and their potential use for nanotechnology applications

Araújo

Milián

Souza

et al. 2019

Cell Biology International

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During pregnancy, the placenta regulates the transfer of oxygen, nutrients, and residual products between the maternal and fetal bloodstreams and is a key determinant of fetal exposure to xenobiotics from the mother. To study the disposition of substances through the placenta, various experimental models are used, especially the perfused placenta, placental villi explants, and cell lineage models. In this context, nanotechnology, an area of study that is on the rise, enables the creation of particles on nanometric scales capable of releasing drugs aimed at specific tissues. An important reason for furthering the studies on transplacental transfer is to explore the potential of nanoparticles (NPs), in new delivery strategies for drugs that are specifically aimed at the mother, the placenta, or the fetus and that involve less toxicity. Due to the fact that the placental barrier is essential for the interaction between the maternal and fetal organisms as well as the possibility of NPs being used in the treatment of various pathologies, the aim of this review is to present the main experimental models used in studying the maternal–fetal interaction and the action of NPs in the placental environment.

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Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production

Cited by 44 publications

References 45 publications

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Macrophage migration inhibitory factor (MIF) promotes rat airway muscle cell proliferation and migration mediated by ERK1/2 and FAK signaling

Experimental models of maternal–fetal interface and their potential use for nanotechnology applications

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