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Effect of estrogen-active compounds on the expression of RACK1 and immunological implicationsBuoso, Erica ...We previously demonstrated the existence of a balance among steroid hormones, i.e. glucocorticoids and androgens, in RACK1 (receptor for activated C kinase 1) expression and innate immunity ... activation, which may offer the opportunity to use RACK1 expression as marker to evaluate immunotoxicity of hormone-active substances. Because of the existence of close interconnections between the different steroid hormone receptors with overlapping ligand specificities and signaling pathways, in this study, we wanted to investigate a possible effect of estrogenic active compounds, namely 17[beta]-estradiol, diethylstilbestrol, and zearalenone, on RACK-1 expression and innate immune responses using THP-1 cells as experimental model. All compounds increased RACK1 transcriptional activity as evaluated by reporter luciferase activity, mRNA expression as assessed by real time-PCR and protein expression by western blot analysis, which paralleled an increase in LPS-induced IL-8, TNF-[alpha] production, and CD86 expression, which we previously demonstrated to be dependent on RACK1/PKC[beta] activation. As the induction of RACK1 expression can be blocked by the antagonist G15, induced by the agonist G1 and by the non-cell permeable 17[beta]-estradiol conjugated with BSA, a role of GPER (previously named GPR30) activation in estrogen-induced RACK1 expression could be demonstrated. In addition, a role of androgen receptor (AR) in RACK1 transcription was also demonstrated by the ability of flutamide, a nonsteroidal antiandrogen, to completely prevent diethylstilbestrol-induced RACK1 transcriptional activity and protein expression. Altogether, our data suggest that RACK1 may represent an interesting target of steroid-active compounds, and its evaluation may offer the opportunity to screen the immunotoxic potential of hormone-active substances.Source: Archives of toxicology. - ISSN 0340-5761 (Vol. 94, 2020, str. 2081-2095)Type of material - article, component part ; adult, seriousPublish date - 2020Language - englishCOBISS.SI-ID - 13047555
Link(s):
https://link.springer.com/article/10.1007/s00204-020-02756-9
https://link.springer.com/content/pdf/10.1007/s00204-020-02756-9.pdfprost dostop preko konzorcija UL
DOI
Author
Buoso, Erica |
Masi, Mirco |
Galbiati, Valentina |
Maddalon, Ambra |
Lulini, Martina |
Kenda, Maša, farmacevtka |
Sollner Dolenc, Marija |
Marinovich, Marina |
Racchi, Marco |
Corsini, Emanuela, pharmacist
Topics
Citokini |
Imunski sistem |
Estrogen |
Citometrija |
Hormoni |
endocrine-disrupting chemicals |
estrogens |
immune system |
hormones |
cytokines |
signal transduction |
signalna transdukcija |
endokrini motilci
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Buoso, Erica | ![]() |
Masi, Mirco | ![]() |
Galbiati, Valentina | ![]() |
Maddalon, Ambra | ![]() |
Lulini, Martina | ![]() |
Kenda, Maša, farmacevtka | 39201 |
Sollner Dolenc, Marija | 08519 |
Marinovich, Marina | ![]() |
Racchi, Marco | ![]() |
Corsini, Emanuela, pharmacist | ![]() |
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