Investigation of host and pathogen responses to oestrogen in cystic fibrosis

Introduction: A ‘gender gap’ exists in cystic fibrosis (CF). Females acquire earlier microbial infections and have a worse prognosis. The sex hormone oestradiol (E2) has recently been highlighted as a key molecule responsible for the CF gender dichotomy. Pseudomonas aeruginosa (Ps. aeruginosa) colonises the CF lung dominating at end stages and undergoes mucoid conversion in response to E2. The aim of this project is to investigate other roles of E2 in host and pathogen, in particular its effects on the growth rate of Ps. aeruginosa and the expression of catalase and superoxide dismutase (SOD) in CF bronchial epithelial cells.

Methods: Growth rate of Ps. aeruginosa (strain PA01) in the presence or absence of E2 was measured by optical density (OD600nm) and by calculating colony-forming units (cfu) per ml. Catalase and SOD gene expression in E2-treated CFBE41o- airway epithelial cells were measured using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results: E2 had no effect on the growth rate of Ps. aeruginosa when compared to control. The expression of catalase mRNA was not altered in CFBE41o- cells in response to E2; however, there was a two-fold increase in SOD gene expression in response to 10nM E2, at 24 hours (p=0.0057).

Conclusion: Oestradiol has no effect on the growth rate of Ps. aeruginosa in vitro. In CF bronchial epithelial cells, although catalase gene expression remains unchanged, E2 increases SOD expression, potentially increasing hydrogen peroxide levels and contributing to Ps. aeruginosa mucoid conversion.