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Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice

Liu, Bo; Henry, Amanda P.; Azimi, Sheyda; Miller, Suzanne; Lee, Frank K.; Lee, Jane C.; Probert, Kelly; Kotlikoff, Michael I.; Sayers, Ian; Hall, Ian P.

Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice Thumbnail


Authors

Bo Liu

Amanda P. Henry

Sheyda Azimi

Dr SUZANNE MILLER suzanne.miller@nottingham.ac.uk
Senior Clinical Studies and Project Manager

Frank K. Lee

Jane C. Lee

Kelly Probert

Michael I. Kotlikoff

IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine



Abstract

Introduction: Genome-Wide Association Studies suggest glutathione S transferase C terminal domain (GSTCD) may play a role in development of Chronic Obstructive Pulmonary Disease. We aimed to define the potential role of GSTCD in airway inflammation and contraction using precision cut lung slice (PCLS) from wild-type (GSTCD+/+) and GSTCD knockout mice (GSTCD-/-).

Methods: PCLS from age and gender matched GSTCD+/+ and GSTCD-/- mice were prepared using a microtome. Contraction was studied after applying either a single dose of Methacholine (Mch) (1 µM) or different doses of Mch (0.001 to 100 µM). Each slice was then treated with lipopolysaccharide (LPS) or vehicle (PBS) for 24 hours. PCLS contraction in the same airway was repeated before and after stimulation. Levels of TNFα production was also measured.

Results: There were no differences in contraction of PCLS from GSTCD+/+ and GSTCD-/- mice in response to Mch (EC50 of GSTCD+/+ vs GSTCD-/- animals: 100.0±20.7 vs 107.7±24.5 nM, p=0.855, n=6 animals/group). However, after LPS treatment, there was a 31.6% reduction in contraction in the GSTCD-/- group (p=0.023, n=6 animals). There was no significant difference between PBS and LPS treatment groups in GSTCD+/+ animals. We observed a significant increase in TNFα production induced by LPS in GSTCD-/- lung slices compared to the GSTCD+/+ LPS treated slices.

Conclusion: GSTCD knockout mice showed an increased responsiveness to LPS (as determined by TNFα production) that was accompanied by a reduced contraction of small airways in PCLS. These data highlight an unrecognised potential function of GSTCD in mediating inflammatory signals that affect airway responses.

Citation

Liu, B., Henry, A. P., Azimi, S., Miller, S., Lee, F. K., Lee, J. C., …Hall, I. P. (2019). Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice. PLoS ONE, 14(9), Article e0221899. https://doi.org/10.1371/journal.pone.0221899

Journal Article Type Article
Acceptance Date Aug 17, 2019
Online Publication Date Sep 12, 2019
Publication Date Sep 12, 2019
Deposit Date Sep 3, 2019
Publicly Available Date Sep 3, 2019
Journal PLos ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 14
Issue 9
Article Number e0221899
DOI https://doi.org/10.1371/journal.pone.0221899
Keywords GSTCD, Precision cut lung slices, Mouse, Lung function
Public URL https://nottingham-repository.worktribe.com/output/2552888
Publisher URL https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221899
Contract Date Sep 3, 2019

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