Exposure to lipopolysaccharide (LPS) reduces contractile response of small airways from GSTCD-/- mice

Autoři: Bo Liu aff001;  Amanda P. Henry aff001;  Sheyda Azimi aff001;  Suzanne Miller aff001;  Frank K. Lee aff002;  Jane C. Lee aff002;  Kelly Probert aff001;  Michael I. Kotlikoff aff002;  Ian Sayers aff001;  Ian P. Hall aff001
Působiště autorů: Division of Respiratory Medicine, & National Institute for Health Medicine, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, England, United Kingdom aff001;  Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221899



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-/-).


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.


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.


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.

Klíčová slova:

Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Mouse models – Animal models – Imaging techniques – Histochemistry and cytochemistry techniques – Immunohistochemistry techniques – Immunologic techniques – Specimen preparation and treatment – Staining – Cell staining – Medicine and health sciences – Pulmonology – Pulmonary function – Chronic obstructive pulmonary disease – Diagnostic medicine – Diagnostic radiology – Pulmonary imaging – Signs and symptoms – Radiology and imaging – Immunology – Immune response – Inflammation – Pathology and laboratory medicine – Biology and life sciences – Organisms – Eukaryota – Animals – Vertebrates – Amniotes – Mammals – Rodents – Mice


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