The effect of statins and the synthetic LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro

He, P; Smith, A; Gelissen, IC; Ammit, AJ

The effect of statins and the synthetic LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro

He, P Smith, A Gelissen, IC Ammit, AJ

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Publication Type:: Journal Article
Citation:: Pharmacological Reports, 2019, 71 (6), pp. 1219 - 1226
Issue Date:: 2019-12-01

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Field	Value	Language
dc.contributor.author	He, P	en_US
dc.contributor.author	Smith, A	en_US
dc.contributor.author	Gelissen, IC	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.date.available	2020-08-18T19:02:22Z
dc.date.issued	2019-12-01	en_US
dc.identifier.citation	Pharmacological Reports, 2019, 71 (6), pp. 1219 - 1226	en_US
dc.identifier.issn	1734-1140	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136780
dc.description.abstract	© 2019 Institute of Pharmacology, Polish Academy of Sciences Background: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with dyslipidemia, an established co-morbidity. Statins treat hypercholesterolemia, but more recently have been trailed in the setting of COPD for their potential anti-inflammatory benefits. The outcomes of prospective trials however have been inconsistent. Thus, we hypothesize that the variation in results may have been due to statin-induced downregulation of ATP-binding cassette transporter A1 (ABCA1), thereby reducing cholesterol export. This study aims to elucidate whether statin treatment in a cellular model of COPD leads to a decrease in ABCA1 protein expression. Methods: To mimic the inflammatory environment of COPD, two commonly used lung epithelial cell lines (BEAS-2B and A549) were treated with tumor necrosis factor (TNF), and co-treated with cholesterol/25-hydroxycholesterol (25-OH) to mimic dyslipidemia. ABCA1 protein was detected by Western Blotting. Results: We unexpectedly showed that statins did not affect ABCA1 expression. However, the LXR agonist T0901317 significantly increased ABCA1 expression in both cell lines, while TNF, cholesterol or 25-OH induced ABCA1 protein upregulation in BEAS-2B cells, indicating cell line differences in response. There was also evidence of synergistic impacts of combined treatments on ABCA1 upregulation in BEAS-2B cells. Conclusion: Statins did not have an impact on ABCA1 expression in lung epithelial cell lines, disproving our original hypothesis. However, we showed for the first time, the effect of the inflammatory cytokine TNF, cholesterol/25-OH, statins and the LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro. We hope that these in vitro studies may prove beneficial for addressing dyslipidemia in COPD in the future.	en_US
dc.relation.ispartof	Pharmacological Reports	en_US
dc.relation.isbasedon	10.1016/j.pharep.2019.08.006	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.title	The effect of statins and the synthetic LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	71	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access	*
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	71	en_US

Abstract:

© 2019 Institute of Pharmacology, Polish Academy of Sciences Background: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with dyslipidemia, an established co-morbidity. Statins treat hypercholesterolemia, but more recently have been trailed in the setting of COPD for their potential anti-inflammatory benefits. The outcomes of prospective trials however have been inconsistent. Thus, we hypothesize that the variation in results may have been due to statin-induced downregulation of ATP-binding cassette transporter A1 (ABCA1), thereby reducing cholesterol export. This study aims to elucidate whether statin treatment in a cellular model of COPD leads to a decrease in ABCA1 protein expression. Methods: To mimic the inflammatory environment of COPD, two commonly used lung epithelial cell lines (BEAS-2B and A549) were treated with tumor necrosis factor (TNF), and co-treated with cholesterol/25-hydroxycholesterol (25-OH) to mimic dyslipidemia. ABCA1 protein was detected by Western Blotting. Results: We unexpectedly showed that statins did not affect ABCA1 expression. However, the LXR agonist T0901317 significantly increased ABCA1 expression in both cell lines, while TNF, cholesterol or 25-OH induced ABCA1 protein upregulation in BEAS-2B cells, indicating cell line differences in response. There was also evidence of synergistic impacts of combined treatments on ABCA1 upregulation in BEAS-2B cells. Conclusion: Statins did not have an impact on ABCA1 expression in lung epithelial cell lines, disproving our original hypothesis. However, we showed for the first time, the effect of the inflammatory cytokine TNF, cholesterol/25-OH, statins and the LXR agonist T0901317 on expression of ABCA1 transporter protein in human lung epithelial cell lines in vitro. We hope that these in vitro studies may prove beneficial for addressing dyslipidemia in COPD in the future.

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