Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells

Tamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like con...

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Main Authors: Maksimiano Rodríguez, John Quiroga, Bayron Cortés, Gabriel Morán, Claudio Henríquez
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2024.1381162/full
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author Maksimiano Rodríguez
John Quiroga
Bayron Cortés
Gabriel Morán
Claudio Henríquez
author_facet Maksimiano Rodríguez
John Quiroga
Bayron Cortés
Gabriel Morán
Claudio Henríquez
author_sort Maksimiano Rodríguez
collection DOAJ
description Tamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like conditions in horses, revealing specific impacts on the innate immune system. While the effects of TAM on equine neutrophils are well-documented, its influence on lymphocytes and the modulation of the immune response polarization remains unclear. This in vitro study employed peripheral blood mononuclear cells (PBMC) from healthy horses, exposing them to varying concentrations of the TAM and assessing the expression of genes involved in the polarization of the immune response (TBX21, IFNG, GATA3, IL4, IL10, FOXP3, and CTLA4) in PBMC stimulated or not with PMA/ionomycin. Additionally, the effect of TAM over the proportion of regulatory T cells (Treg) was also assessed. TAM did not significantly affect the expression of these genes and Treg at low concentrations. However, at the highest concentration, there was an impact on the expression of GATA3, IL4, IL10, and CTLA4 genes. These alterations in genes associated with a Th2 and regulatory response coincided with a noteworthy increase in drug-associated cytotoxicity but only at concentrations far beyond those achieved in pharmacological therapy. These findings suggest that the effects of TAM, as described in preclinical studies on asthmatic horses, may not be attributed to the modification of the adaptive response.
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spelling doaj.art-d34b91fb2a6b42cfaf9cc96c05e2f20d2024-04-10T13:32:35ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692024-04-011110.3389/fvets.2024.13811621381162Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cellsMaksimiano RodríguezJohn QuirogaBayron CortésGabriel MoránClaudio HenríquezTamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like conditions in horses, revealing specific impacts on the innate immune system. While the effects of TAM on equine neutrophils are well-documented, its influence on lymphocytes and the modulation of the immune response polarization remains unclear. This in vitro study employed peripheral blood mononuclear cells (PBMC) from healthy horses, exposing them to varying concentrations of the TAM and assessing the expression of genes involved in the polarization of the immune response (TBX21, IFNG, GATA3, IL4, IL10, FOXP3, and CTLA4) in PBMC stimulated or not with PMA/ionomycin. Additionally, the effect of TAM over the proportion of regulatory T cells (Treg) was also assessed. TAM did not significantly affect the expression of these genes and Treg at low concentrations. However, at the highest concentration, there was an impact on the expression of GATA3, IL4, IL10, and CTLA4 genes. These alterations in genes associated with a Th2 and regulatory response coincided with a noteworthy increase in drug-associated cytotoxicity but only at concentrations far beyond those achieved in pharmacological therapy. These findings suggest that the effects of TAM, as described in preclinical studies on asthmatic horses, may not be attributed to the modification of the adaptive response.https://www.frontiersin.org/articles/10.3389/fvets.2024.1381162/fulltamoxifenhorseT lymphocytesimmune response polarizationT regulatory cellscytotoxicity
spellingShingle Maksimiano Rodríguez
John Quiroga
Bayron Cortés
Gabriel Morán
Claudio Henríquez
Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
Frontiers in Veterinary Science
tamoxifen
horse
T lymphocytes
immune response polarization
T regulatory cells
cytotoxicity
title Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
title_full Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
title_fullStr Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
title_full_unstemmed Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
title_short Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
title_sort effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells
topic tamoxifen
horse
T lymphocytes
immune response polarization
T regulatory cells
cytotoxicity
url https://www.frontiersin.org/articles/10.3389/fvets.2024.1381162/full
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