Dimorphic effect of 17β-oestradiol on pathology and oxidative stress in experimental malaria

Aguilar-Castro, Jesús; Cervantes-Candelas, Luis Antonio; Buendía-González, Fidel Orlando; Nolasco-Pérez, Teresita de Jesús; López-Padilla, Monserrat Sofía; Fernández-Rivera, Omar; Cervantes-Sandoval, Armando; Legorreta-Herrera, Martha

doi:10.1016/j.imbio.2019.11.008

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…Previously, under the same experimental conditions, it has been demonstrated that 17β-E2 determines its maximum anti-apoptotic and anti-osteoclastogenic effect without diminishing ROS levels [43]. In addition, in starved MLO-Y4 cells, it has been demonstrated that 10 nM 17β-E2 shows a weak antioxidant effect only after 24 h, not due to a direct ROS scavenger effect, but mostly due to its ability to up-regulate antioxidant enzymes which requires longer times [43,[59][60][61]. For this reason, 17β-E2 does not prevents early apoptosis and up-regulation of active FGF23 through its antioxidant ability, which, however, can contribute to the normalization of FGF23 levels only after 48 h. Therefore, 17β-E2 can immediately contribute to maintenance of normal bone metabolism rate through non-redox-regulated mechanisms, even in the presence of oxidative stress.…”

Section: Discussionmentioning

confidence: 93%

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Domazetovic

Falsetti

Ciuffi

et al. 2022

IJMS

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The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β–estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β–estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.

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Section: Discussionmentioning

confidence: 93%

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Domazetovic

Falsetti

Ciuffi

et al. 2022

IJMS

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“…In addition, 17β-oestradiol administration to intact female mice infected with P. berghei ANKA increases parasitaemia and decreases body weight. By contrast, reconstitution of gonadectomised female mice using 17β-oestradiol reduces parasitaemia and affects the immune response [19,20].…”

Section: Introductionmentioning

confidence: 97%

Tamoxifen Suppresses the Immune Response to Plasmodium berghei ANKA and Exacerbates Symptomatology

et al. 2021

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Malaria is the most lethal parasitic disease in the world. Mortality and severity in symptoms are higher in men than women, suggesting that oestrogens, which are in higher concentration in females than in males, may regulate the immune response against malaria. Tamoxifen, a selective oestrogen receptor modulator used in breast cancer treatment due to its antagonistic effect on oestrogen receptors α and β, is also studied because of its potential therapeutic use for several parasitic diseases. However, most studies, including one in malaria, have not addressed the immunomodulatory role of tamoxifen. In this work, we evaluated the effect of tamoxifen on the immune response of CBA/Ca mice against Plasmodium berghei ANKA. This study showed for the first time that tamoxifen increased parasite load, aggravated symptoms by decreasing body temperature and body weight, and worsened anaemia. Additionally, tamoxifen significantly increased the splenic index and the percentages of CD4+ and NK+ cells on day eight post-infection. By contrast, tamoxifen decreased both CD8+ and B220+ populations in the spleen and decreased the serum levels of IL-2, IL-6, and IL-17. Our findings support the notion that tamoxifen is a potent immunomodulator in malaria-infected mice and suggest caution when administering it to malaria-infected women with breast cancer.

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“…Male or female mice were subcutaneously injected with 545 µg of 17b-estradiol/kg of body weight (approximately 12 µg/mouse) in 50 µL of sesame oil (vehicle) twice a week for three weeks as previously described by Benten et al (12). By using this 17bestradiol concentration, we have previously showed 17bestradiol effects on oxidative stress (17).…”

Section: B-estradiol Administration and Parasitemiamentioning

confidence: 99%

17β-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria

et al. 2021

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Malaria is the leading cause of parasitic infection-related death globally. Additionally, malaria-associated mortality is higher in men than in women, and this sexual dimorphism reflects differences in innate and adaptive immune responses that are influenced by sex hormones. Normally, females develop more robust immune responses against parasites than males. However, most clinical and laboratory studies related to the immune response to malaria do not consider sex as a variable, and relatively few studies have compared the sex-dependent role of 17β-estradiol in this process. In this study, we decreased in vivo the levels of 17β-estradiol by gonadectomy or administered 17β-estradiol to intact or gonadectomized male and female CBA/Ca mice infected with Plasmodium berghei ANKA. Subsequently, we assessed the effects of 17β-estradiol on parasite load; the percentages of different immune cells in the spleen; the plasma levels of antibodies and pro- and anti-inflammatory cytokines; and the mRNA expression levels of cytokine-encoding genes in the brain. The results showed that the administration of 17β-estradiol increased parasitemia and decreased body weight in intact female mice. Moreover, intact females exhibited higher levels of CD8+ T cells and lower levels of NK1.1+ cells than their male counterparts under the same condition. Gonadectomy increased IFN-γ and decreased TNF-α concentrations only in intact female mice. Additionally, IL-10 levels were higher in intact females than in their male counterparts. Finally, the mRNA expression levels of cytokines coding genes in the brain showed a dimorphic pattern, i.e., gonadectomy upregulated Tnf, Il1b, and Il10 expression in males but not in females. Our findings explain the sexual dimorphism in the immune response to malaria, at least in part, and suggest potential sex-dependent implications for the efficacy of vaccines or drugs targeting malaria.

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Dimorphic effect of 17β-oestradiol on pathology and oxidative stress in experimental malaria

Cited by 4 publications

References 46 publications

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Tamoxifen Suppresses the Immune Response to Plasmodium berghei ANKA and Exacerbates Symptomatology

17β-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria

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