Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes
- Autores
- Zappia, Carlos Daniel; Torralba Agu, Valeria Nora; Echeverría, Emiliana Beatriz; Fitzsimons, Carlos P.; Fernandez, Natalia Cristina; Monczor, Federico
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell-and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.
Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Torralba Agu, Valeria Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Echeverría, Emiliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Fitzsimons, Carlos P.. Swammerdam Institute For Life Sciences; Países Bajos
Fil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina - Materia
-
ANTIHISTAMINES
DEXAMETHASONE
GLUCOCORTICOIDS
HISTAMINE
INFLAMMATION - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/176655
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Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genesZappia, Carlos DanielTorralba Agu, Valeria NoraEcheverría, Emiliana BeatrizFitzsimons, Carlos P.Fernandez, Natalia CristinaMonczor, FedericoANTIHISTAMINESDEXAMETHASONEGLUCOCORTICOIDSHISTAMINEINFLAMMATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell-and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Torralba Agu, Valeria Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Echeverría, Emiliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Fitzsimons, Carlos P.. Swammerdam Institute For Life Sciences; Países BajosFil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaMDPI2021-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/176655Zappia, Carlos Daniel; Torralba Agu, Valeria Nora; Echeverría, Emiliana Beatriz; Fitzsimons, Carlos P.; Fernandez, Natalia Cristina; et al.; Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes; MDPI; Cells; 10; 11; 11-2021; 1-152073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/cells10113026info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:17Zoai:ri.conicet.gov.ar:11336/176655instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:18.036CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
title |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
spellingShingle |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes Zappia, Carlos Daniel ANTIHISTAMINES DEXAMETHASONE GLUCOCORTICOIDS HISTAMINE INFLAMMATION |
title_short |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
title_full |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
title_fullStr |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
title_full_unstemmed |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
title_sort |
Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes |
dc.creator.none.fl_str_mv |
Zappia, Carlos Daniel Torralba Agu, Valeria Nora Echeverría, Emiliana Beatriz Fitzsimons, Carlos P. Fernandez, Natalia Cristina Monczor, Federico |
author |
Zappia, Carlos Daniel |
author_facet |
Zappia, Carlos Daniel Torralba Agu, Valeria Nora Echeverría, Emiliana Beatriz Fitzsimons, Carlos P. Fernandez, Natalia Cristina Monczor, Federico |
author_role |
author |
author2 |
Torralba Agu, Valeria Nora Echeverría, Emiliana Beatriz Fitzsimons, Carlos P. Fernandez, Natalia Cristina Monczor, Federico |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
ANTIHISTAMINES DEXAMETHASONE GLUCOCORTICOIDS HISTAMINE INFLAMMATION |
topic |
ANTIHISTAMINES DEXAMETHASONE GLUCOCORTICOIDS HISTAMINE INFLAMMATION |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell-and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy. Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Torralba Agu, Valeria Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Echeverría, Emiliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Fitzsimons, Carlos P.. Swammerdam Institute For Life Sciences; Países Bajos Fil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina |
description |
Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell-and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/176655 Zappia, Carlos Daniel; Torralba Agu, Valeria Nora; Echeverría, Emiliana Beatriz; Fitzsimons, Carlos P.; Fernandez, Natalia Cristina; et al.; Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes; MDPI; Cells; 10; 11; 11-2021; 1-15 2073-4409 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/176655 |
identifier_str_mv |
Zappia, Carlos Daniel; Torralba Agu, Valeria Nora; Echeverría, Emiliana Beatriz; Fitzsimons, Carlos P.; Fernandez, Natalia Cristina; et al.; Antihistamines potentiate dexamethasone anti-inflammatory effects: Impact on glucocorticoid receptor-mediated expression of inflammation-related genes; MDPI; Cells; 10; 11; 11-2021; 1-15 2073-4409 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.3390/cells10113026 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.13397 |