Glucocorticoid agonistic and antagonistic effects of mifepristone and onapristone on thymocyte subset composition and CD26/dipeptidyl peptidase IV activity in infant male rats

Kraml, J; Kolínská, J; Sinkora, J; Zákostelecká, Marie; Kadlecová, L; D, Hirsová; Nosková, Lenka

doi:10.1016/j.jsbmb.2003.07.002

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…Mice injected with rAAV-BDNF or rAAV-YFP were split to receive mifepristone or vehicle and housed in SE. Consistent with published data (21), mifepristone administration to rAAV-YFP mice led to lower thymus weight and thymocyte number compared to rAAV-YFP mice receiving vehicle ( fig. S6A, B ).…”

Section: Resultssupporting

confidence: 92%

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

Xiao

Bergin

Huang

et al. 2019

Brain, Behavior, and Immunity

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Environmental and social factors have profound impacts on immune homeostasis. Our work on environmental enrichment (EE) has revealed a novel anti-obesity and anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues. Here we investigated how an EE modulated thymus and thymocyte development. EE decreased thymus mass and cellularity, decreased the double positive thymocyte population, increased the proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69 expression in T cells. In a model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord inflammation through regulation of type 1 T-helper cells mediated by glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance. Our mechanistic studies demonstrated that hypothalamic BDNF activated a hypothalamic-pituitary-adrenal axis mediating the EE’s thymic effects. Our results indicate that a lifestyle intervention links the nervous, endocrine, and adaptive immune system, allowing the body to adapt to internal and external environments.

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Section: Resultssupporting

confidence: 92%

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

Xiao

Bergin

Huang

et al. 2019

Brain, Behavior, and Immunity

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“…RU486 was shown to inhibit the translocation of GR to the nucleus in rat thymocytes (Lefebvre et al, 1988) and also to stabilise the the association of GR to Hsp-90 in mouse lymphoma cells (Distelhorst and Howard, 1990). On the other hand, the translocation of GR to the nucleus was described upon RU486 treatment (Pariante et al, 2001;Schaaf and Cidlowski, 2003), and the partial GR agonistic effect of RU486 was also shown (Kraml et al, 2003;Nordeen et al, 1993), suggesting that the GR antagonist effect of RU486 is dependent on the experimental system and cell/tissue type, respectively. According to our data, RU486 could not block the early (within 8 h) transcriptional autoregulatory activity of the GR in mouse thymocytes, in vivo, but the exact mechanism of this needs further elucidation.…”

Section: Article In Pressmentioning

confidence: 99%

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

et al. 2006

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“…Onapristone is considered to be pure antagonist of PR. It shows only minimal affinity to GR [12], however in vivo studies in rats may suggest its potential agonistic and antagonistic action on GR [32]. …”

Section: Discussionmentioning

confidence: 99%

Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

et al. 2013

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BackgroundAglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Its molecular structure is similar to mifepristone, an antiprogestin used in human medicine. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral blood mononuclear cells (PBMCs) were incubated with three different dosages of aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The production of cytokines by resting or mitogen-activated T cells was determined by intercellular staining and flow cytometry analysis or ELISA assay, respectively.ResultsOur results showed no statistically significant differences in the percentage of IFN-γ and IL-4-synthesizing CD4+ or CD8+ resting T cells between untreated and aglepristone-treated cells at 24 and 48 hours post treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar concentration of IFN-γ and IL-4 in culture supernatants to those observed in mitogen-activated DMSO-treated PBMCs. Presented results indicate that administration of aglepristone for 48 hours has no influence on IFN-γ and IL-4 synthesis by resting and mitogen-activated T cells isolated from diestral bitches.ConclusionsWe conclude that antiprogestins may differentially affect T cell function depending on the animal species in which they are applied.

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Glucocorticoid agonistic and antagonistic effects of mifepristone and onapristone on thymocyte subset composition and CD26/dipeptidyl peptidase IV activity in infant male rats

Cited by 8 publications

References 65 publications

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

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