Open AccessExposure to lipopolysaccharide (LPS) reduces contractile response of small airways from GSTCD-/- mice
Author(s) -
Bo Liu,
Amanda Henry,
Sheyda Azimi,
Suzanne Miller,
Frank K. Lee,
Jane C. Lee,
Kelly Probert,
Michael I. Kotlikoff,
Ian Sayers,
Ian Hall
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221899
Subject(s) - lipopolysaccharide , contraction (grammar) , methacholine , medicine , stimulation , endocrinology , inflammation , chemistry , knockout mouse , lung , immunology , respiratory disease , receptor
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 (EC 50 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.