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.

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., Probert, K., Kotlikoff, M. I., Sayers, I., & 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