Gender differences in transcriptional regulation of IL-5 expression by bronchial lymph node cells in a mouse model of asthma.

ABSTRACT

BACKGROUND AND OBJECTIVE: The severity of asthma after puberty is higher in women than in men. Increased numbers of eosinophils in the airways of female mice after antigen challenge was associated with increased levels of T helper (Th)2 cytokines at the site of inflammation, and in human and mouse studies, the profile of cytokines produced by immune cells from women showed greater Th2 predominance. The aim of this study was to investigate gender differences in the development of Th2 immune responses. METHODS: Male and female C57BL/6 mice were sensitized with ovalbumin. Cells prepared from bronchial lymph nodes were cultured in the absence or presence of ovalbumin. Cytokine concentrations in the culture supernatants were measured, and IL-5 and GATA-binding protein 3 (GATA-3) gene expression were evaluated. T-cell subsets were analysed using specific surface markers. RESULTS: The concentrations of IL-4, IL-5, IL-13 and IL-10, but not interferon-gamma or transforming growth factor-beta(1), were higher in cell supernatants from female mice than in those from male mice. IL-5 and GATA-3 gene expressions were higher in cells from women than in cells from men. The numbers of CD3(+)CD4(+)T1/ST2(+) cells, but not CD3(+)CD4(+) or CD4(+)CD25(+) cells, were significantly higher in cells from women than in cells from men. CONCLUSIONS: Greater antigen-induced Th2 cytokine production by bronchial lymph node cells from female mice was associated with enhanced Th2 cell differentiation and increased expression of the Th2-specific transcription factor, GATA-3.