Effect of MP-AzeFlu compared to monotherapy on COX-2, PGE2 , and EP2 gene expression in upper airway mucosa
Sonia Vicens-Artes1, Jordi Roca-Ferrer1,2, Valeria Tubita1,3
1Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, Barcelona, Spain.
Abstract:
MP-AzeFlu (intranasal fluticasone and azelastine) has been widely studied and has demonstrated efficacy in Allergic rhinitis with a superior effect compared to these drugs administered individually; however, the mechanism by which MP-AzeFlu produces this improved clinical effect has not yet been fully explained. In this study, we investigated the effect of MP-AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism as measured by changes in regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D2 , PGE2 , PGE2 receptor (EP) 2, and EP3. Expression of these key inflammation markers was assessed through an in vitro model of upper airway inflammation using fibroblasts derived from both healthy and inflamed upper airway mucosa. Both MP-AzeFlu and FP inhibited interleukin-1β-induced COX-2 messenger RNA (mRNA) and protein expression and PGE2 secretion in vitro. MP-AzeFlu and FP both upregulated EP2 mRNA expression, though neither upregulated EP2 protein expression. This downregulation of COX-2 and PGE2 coupled with upregulation of EP2 receptor expression reinforces the anti-inflammatory effect of MP-AzeFlu in upper airway inflammation.
Insights
Intranasal fluticasone and azelastine (MP-AzeFlu) reduces upper airway inflammation by downregulating cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). This combination therapy also upregulates the EP2 receptor, enhancing its anti-inflammatory effects.
Area of Science:
- Immunology
- Pharmacology
- Otolaryngology
Background:
- Allergic rhinitis treatment often involves intranasal corticosteroids and antihistamines.
- MP-AzeFlu (intranasal fluticasone and azelastine) shows superior efficacy compared to individual components for allergic rhinitis.
- The precise anti-inflammatory mechanisms of MP-AzeFlu remain incompletely understood.
Purpose of the Study:
- To investigate the effects of MP-AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism.
- To assess the regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D2, PGE2, and prostaglandin E2 receptors (EP2, EP3) in vitro.
- To elucidate the molecular mechanisms underlying the enhanced clinical effect of MP-AzeFlu.
Main Methods:
- Utilized an in vitro model of upper airway inflammation with fibroblasts from healthy and inflamed nasal mucosa.
- Assessed the expression of COX-2 mRNA and protein, and PGE2 secretion following interleukin-1β stimulation.
- Evaluated the regulation of EP2 and EP3 receptor mRNA and protein expression.
Main Results:
- Both MP-AzeFlu and FP significantly inhibited interleukin-1β-induced COX-2 mRNA and protein expression.
- MP-AzeFlu and FP reduced PGE2 secretion in vitro.
- Both treatments upregulated EP2 receptor mRNA expression, but not protein expression.
Conclusions:
- MP-AzeFlu and FP demonstrate anti-inflammatory effects by downregulating COX-2 and PGE2 pathways.
- The upregulation of EP2 receptor mRNA by MP-AzeFlu may contribute to its enhanced efficacy in managing upper airway inflammation.
- These findings provide mechanistic insights into the superior clinical outcomes observed with MP-AzeFlu in allergic rhinitis.
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