| Popis: |
Women are more likely to have severe asthma than men. Recent data suggest this could be due to women having more circulating CD4+CRTh2+ T cells (Th2 cells). Glucocorticosteroids (GC)s are the main therapy for asthma as they inhibit cytokine production and eliminate inflammatory cells by apoptosis. The current study examined whether the female sex hormone estrogen influences the anti-inflammatory action of GC. Experiments show that ER⍺ agonist reduced GC-induced apoptosis of primary Th2 cells and enhanced GC-mediated transcriptional activation of the proximal CRTh2 promoter. Genetic variation within CRTh2 is associated with asthma and allergic phenotypes. Using constructs representing the single nucleotide polymorphism CRTh2-6388G>A, ER⍺ agonist enhanced GC-induced activity of the A but not the G allele. Collectively, these data suggest that in vivo Th2 cells may exhibit sex and genotype specific response to GC and that some of these effects are pro-inflammatory. |
