Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
Autor: | Emiliana Beatriz Echeverría, Federico Monczor, Natalia Fernández, Carlos Daniel Zappia, Valeria Torralba-Agu, Carlos P. Fitzsimons |
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Přispěvatelé: | Structural and Functional Plasticity of the nervous system (SILS, FNWI) |
Rok vydání: | 2021 |
Předmět: |
antihistamines
QH301-705.5 medicine.medical_treatment Anti-Inflammatory Agents Histamine Antagonists dexamethasone Inflammation Pharmacology Bone and Bones Article Cell Line Mice chemistry.chemical_compound Receptors Glucocorticoid Glucocorticoid receptor Genes Reporter medicine Animals Humans Biology (General) Adverse effect Dexamethasone Cell Proliferation Regulation of gene expression Osteoblasts glucocorticoids Tumor Necrosis Factor-alpha business.industry NF-kappa B General Medicine histamine Effective dose (pharmacology) Gene Expression Regulation chemistry inflammation Phthalazines Antihistamine medicine.symptom business Biomarkers Histamine medicine.drug |
Zdroj: | Cells Volume 10 Issue 11 Cells, 10(11):3026. MDPI Cells, Vol 10, Iss 3026, p 3026 (2021) |
ISSN: | 2073-4409 |
Popis: | 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. |
Databáze: | OpenAIRE |
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