Annexin A1 peptide is able to induce an anti-parasitic effect in human placental explants infected by Toxoplasma gondii

Cardoso, Marystela Fávero de Oliveira; Moreli, Jusciéle Brogin; Gomes, A. da S.; Zanon, Caroline de Freitas; Silva, Ana Elizabete; Paulesu, Luana; Ietta, Francesca; Mineo, José Roberto; Ferro, Eloísa Amália Vieira; Oliani, Sônia Maria

doi:10.1016/j.micpath.2018.07.005

Cited by 16 publications

(10 citation statements)

References 34 publications

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“…We observed that both inhibitors did not alter the viability of human villous explants and were also able to strongly reduce the T. gondii intracellular proliferation. Studies demonstrate that the annexin A1 peptide was able to reduce parasitism in villous explants infected by T. gondii , and this was related to a decrease in COX-2/PGE 2 production 84 . Regarding to cytokines production, we observed that only infected villous decreased the MIF production and increased IL-10, suggesting a possible escape mechanism for T. gondii , besides inducing a high production of TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Souza

Silva

Milián

et al. 2021

Sci Rep

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Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-β1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.

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Section: Discussionmentioning

confidence: 99%

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Souza

Silva

Milián

et al. 2021

Sci Rep

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“…Also, our previous study showed that human trophoblast cells treated with PGE 2 presented higher susceptibility to T. gondii infection (RH strain), evidencing that PGE 2 can facilitate parasite proliferation (Barbosa et al, 2014). Additionally, it was demonstrated that annexin A1 decreased parasitism rate in human placenta infected by T. gondii and it was associated with reduced levels of PGE 2 and COX-2 (Oliveira-Cardoso et al, 2018). Thus, to control the parasite replication, the host cells should reduce COX-2 expression to dampen the T. gondii susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase (COX)-2 Inhibitors Reduce Toxoplasma gondii Infection and Upregulate the Pro-inflammatory Immune Response in Calomys callosus Rodents and Human Monocyte Cell Line

Aca

Silva

et al. 2019

Front. Microbiol.

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Toxoplasma gondii is able to infect a wide range of vertebrates, including humans. Studies show that cyclooxygenase-2 (COX-2) is a modulator of immune response in multiple types of infection, such as Trypanosoma cruzi . However, the role of COX-2 during T. gondii infection is still unclear. The aim of this study was to investigate the role of COX-2 during infection by moderately or highly virulent strains of T. gondii in Calomys callosus rodents and human THP-1 cells. C. callosus were infected with 50 cysts of T. gondii (ME49), treated with COX-2 inhibitors (meloxicam or celecoxib) and evaluated to check body weight and morbidity. After 40 days, brain and serum were collected for detection of T. gondii by real-time PCR and immunohistochemistry or cytokines by CBA. Furthermore, peritoneal macrophages or THP-1 cells, infected with RH strain or uninfected, were treated with meloxicam or celecoxib to evaluate the parasite proliferation by colorimetric assay and cytokine production by ELISA. Finally, in order to verify the role of prostaglandin E 2 in COX-2 mechanism, THP-1 cells were infected, treated with meloxicam or celecoxib plus PGE 2 , and analyzed to parasite proliferation and cytokine production. The data showed that body weight and morbidity of the animals changed after infection by T. gondii , under both treatments. Immunohistochemistry and real-time PCR showed a reduction of T. gondii in brains of animals treated with both COX-2 inhibitors. Additionally, it was observed that both COX-2 inhibitors controlled the T. gondii proliferation in peritoneal macrophages and THP-1 cells, and the treatment with PGE 2 restored the parasite growth in THP-1 cells blocked to COX-2. In the serum of Calomys , upregulation of pro-inflammatory cytokines was detected, while the supernatants of peritoneal macrophages and THP-1 cells demonstrated significant production of TNF and nitrite, or TNF, nitrite and MIF, respectively, under both COX-2 inhibitors. Finally, PGE 2 treatment in THP-1 cells triggered downmodulation of pro-inflammatory mediators and upregulation of IL-8 and IL-10. Thus, COX-2 is an immune mediator involved in the susceptibility to T. gondii regardless of strain or cell types, since inhibition of this enzyme induced control of infection by upregulating important pro-inflammatory mediators against Toxoplasma .

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“…Abnormal GC metabolism is also responsible for spontaneous miscarriages [ 19 ]. GC activity is mediated by the calcium-dependent phospholipid binding protein, Annexin A1 (ANXA1) [ 20 ]. Nevertheless, the potential applications for lipoxin A4 in the area of reproductive biology remain unexplored and require further research (Fig.…”

Section: Introductionmentioning

confidence: 99%

Changes of lipoxin levels during pregnancy and the monthly-cycle, condition the normal course of pregnancy or pathology

et al. 2020

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Objective and Design The purpose of the review was to gather information on the role and possibilities of using lipoxin in the treatment of infertility and maintaining a normal pregnancy. Ovulation, menstruation, embryo implantation, and childbirth are reactions representing short-term inflammatory events involving lipoxin activities. Lipoxin A4 (LXA4) is an arachidonic acid metabolite, and in cooperation with its positional isomer lipoxin B4 (LXB4), it is a major lipoxin in mammals. Biosynthesis process occurs in two stages: in the first step, the donor cell releases the eicosanoid intermediate; secondarily, the acceptor cell gets and converts the intermediate product into LXA4 (leukocyte/platelet interaction). Results Generating lipoxin synthesis may also be triggered by salicylic acid, which acetylates cyclooxygenase-2. Lipoxin A4 and its analogues are considered as specialized pro-resolving mediators. LXA4 is an important component for a proper menstrual cycle, embryo implantation, pregnancy, and delivery. Its level in the luteal phase is high, while in the follicular phase, it decreases, which coincides with an increase in estradiol concentration with which it competes for the receptor. LXA4 inhibits the progression of endometriosis. However, during the peri-implantation period, before pregnancy is confirmed clinically, high levels of LXA4 can contribute to early pregnancy loss and may cause miscarriage. After implantation, insufficient LXA4 levels contribute to incorrect maternal vessel remodeling; decreased, shallow trophoblastic invasion; and the immuno-energetic abnormality of the placenta, which negatively affects fetal growth and the maintenance of pregnancy. Moreover, the level of LXA4 increases in the final stages of pregnancy, allowing vessel remodeling and placental separation. Methods The review evaluates the literature published in the PubMed and Embase database up to 31 December 2019. The passwords were checked on terms: lipoxin and pregnancy with combined endometriosis, menstrual cycle, implantation, pre-eclampsia, fetal growth restriction, and preterm labor. Conclusions Although no human studies have been performed so far, the cell and animal model study results suggest that LXA4 will be used in obstetrics and gynecology soon.

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Annexin A1 peptide is able to induce an anti-parasitic effect in human placental explants infected by Toxoplasma gondii

Cited by 16 publications

References 34 publications

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants

Cyclooxygenase (COX)-2 Inhibitors Reduce Toxoplasma gondii Infection and Upregulate the Pro-inflammatory Immune Response in Calomys callosus Rodents and Human Monocyte Cell Line

Changes of lipoxin levels during pregnancy and the monthly-cycle, condition the normal course of pregnancy or pathology

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