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

Autor: Jane C. Lee, Bo Liu, Frank K. Lee, Sheyda Azimi, Ian P. Hall, Michael I. Kotlikoff, Suzanne Miller, Amanda P. Henry, Ian Sayers, Kelly Probert
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
Contraction (grammar)
Pulmonology
Lipopolysaccharide
Pulmonary Function
Stimulation
Pathology and Laboratory Medicine
Diagnostic Radiology
Gene Knockout Techniques
Mice
chemistry.chemical_compound
0302 clinical medicine
Medicine and Health Sciences
Immune Response
Methacholine Chloride
Glutathione Transferase
Staining
Mammals
Multidisciplinary
Radiology and Imaging
Cell Staining
Eukaryota
Animal Models
Pulmonary Imaging
Up-Regulation
3. Good health
medicine.anatomical_structure
Experimental Organism Systems
Vertebrates
Knockout mouse
Medicine
Female
Tumor necrosis factor alpha
medicine.symptom
Muscle Contraction
Research Article
medicine.drug
medicine.medical_specialty
Imaging Techniques
Chronic Obstructive Pulmonary Disease
Science
Immunology
Mouse Models
Inflammation
Research and Analysis Methods
Rodents
03 medical and health sciences
Model Organisms
Signs and Symptoms
Diagnostic Medicine
Internal medicine
medicine
Animals
Bronchioles
Immunohistochemistry Techniques
Lung
Tumor Necrosis Factor-alpha
Organisms
Biology and Life Sciences
Histochemistry and Cytochemistry Techniques
Disease Models
Animal
030104 developmental biology
Endocrinology
030228 respiratory system
chemistry
Specimen Preparation and Treatment
Amniotes
Animal Studies
Immunologic Techniques
Methacholine
Zdroj: PLoS ONE, Vol 14, Iss 9, p e0221899 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: IntroductionGenome-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-/-).MethodsPCLS 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.ResultsThere 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.ConclusionGSTCD 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.
Databáze: OpenAIRE
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