| First Author | Liu B | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 9 | Pages | e0221899 |
| PubMed ID | 31513609 | Mgi Jnum | J:279480 |
| Mgi Id | MGI:6360828 | Doi | 10.1371/journal.pone.0221899 |
| Citation | Liu B, et al. (2019) Exposure to lipopolysaccharide (LPS) reduces contractile response of small airways from GSTCD-/- mice. PLoS One 14(9):e0221899 |
| abstractText | 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 muM) or different doses of Mch (0.001 to 100 muM). 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 TNFalpha 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 TNFalpha 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 TNFalpha 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. |
