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Investigation of host and pathogen responses to estrogen in cystic fibrosis

Introduction

A ‘gender gap’ exists in Cystic Fibrosis (CF). Females acquire earlier microbial infections; have worse lung function and poorer survival rates [1]. The sex-hormone estrogen (estradiol, E2) has recently been highlighted as a key molecule responsible for the CF gender dichotomy [2]. Pseudomonas aeruginosa which colonises the CF lung and dominates at end stage disease undergoes mucoid conversion in response to E2 [2, 3]. The aim of this project was to study other roles of E2 in host and pathogen responses by investigating 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 (PA01) in the presence or absence of E2 was measured by recording optical density (OD 600nm) at different time points and by calculating cfu/ml. Measurements of catalase and SOD gene expression in E2-treated CFBE410- airway epithelial cells were carried out using real time qRT-PCR. Results were analysed using Graphpad PRISM 5.0.

Results

E2 had no effect on the growth of Ps. aeruginosa when compared to control. The expression of catalase mRNA in CFBE410- cells in response to E2 was not altered however, there was two-fold increase in SOD gene expression in response to 10 nM E2, 24hr (p= 0.0057).

Conclusion

Estradiol has no effect on the growth 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.

References

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  2. Chotirmall SC, Harvey BJ, McElvaney NG, Greene CM: Pulmonary Inflammation in Cystic Fibrosis. Current Medical Literature – Cystic Fibrosis. 2011, 2: 37-48.

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  3. Chotirmall SH, Smith SG, O'Neill SJ, Greene CM, McElvaney NG, et al: Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med. 2012, 366 (21): 1978-86. 10.1056/NEJMoa1106126. 24

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Correspondence to Moyser Mulla.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mulla, M., Lavelle, G., McKiernan, P. et al. Investigation of host and pathogen responses to estrogen in cystic fibrosis. BMC Proc 7 (Suppl 1), P4 (2013). https://doi.org/10.1186/1753-6561-7-S1-P4

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  • DOI: https://doi.org/10.1186/1753-6561-7-S1-P4

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