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.

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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