Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

dc.contributor.author

Ingram, Jennifer L

dc.contributor.author

Slade, David

dc.contributor.author

Church, Tony D

dc.contributor.author

Francisco, Dave

dc.contributor.author

Heck, Karissa

dc.contributor.author

Sigmon, R Wesley

dc.contributor.author

Ghio, Michael

dc.contributor.author

Murillo, Anays

dc.contributor.author

Firszt, Rafael

dc.contributor.author

Lugogo, Njira L

dc.contributor.author

Que, Loretta

dc.contributor.author

Sunday, Mary E

dc.contributor.author

Kraft, Monica

dc.date.accessioned

2022-07-01T15:04:18Z

dc.date.available

2022-07-01T15:04:18Z

dc.date.issued

2016-01

dc.date.updated

2022-07-01T15:04:17Z

dc.description.abstract

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

dc.identifier.issn

1044-1549

dc.identifier.issn

1535-4989

dc.identifier.uri

https://hdl.handle.net/10161/25437

dc.language

eng

dc.publisher

American Thoracic Society

dc.relation.ispartof

American journal of respiratory cell and molecular biology

dc.relation.isversionof

10.1165/rcmb.2014-0290oc

dc.subject

Lung

dc.subject

Elastic Tissue

dc.subject

Fibroblasts

dc.subject

Humans

dc.subject

Asthma

dc.subject

Elastin

dc.subject

Interleukin-13

dc.subject

Bronchial Provocation Tests

dc.subject

Vital Capacity

dc.subject

Forced Expiratory Volume

dc.subject

Severity of Illness Index

dc.subject

Case-Control Studies

dc.subject

Signal Transduction

dc.subject

Down-Regulation

dc.subject

Adult

dc.subject

North Carolina

dc.subject

Colorado

dc.subject

Female

dc.subject

Male

dc.subject

Matrix Metalloproteinase 2

dc.subject

Matrix Metalloproteinase 1

dc.subject

Airway Remodeling

dc.subject

Matrix Metalloproteinase Inhibitors

dc.title

Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

dc.type

Journal article

duke.contributor.orcid

Ingram, Jennifer L|0000-0002-5269-8864

pubs.begin-page

41

pubs.end-page

50

pubs.issue

1

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Faculty

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Cell Biology

pubs.organisational-group

Medicine

pubs.organisational-group

Pathology

pubs.organisational-group

Pediatrics

pubs.organisational-group

Surgery

pubs.organisational-group

Medicine, Pulmonary, Allergy, and Critical Care Medicine

pubs.organisational-group

Surgery, Surgical Sciences

pubs.publication-status

Published

pubs.volume

54

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
rcmb.2014-0290oc.pdf
Size:
1.13 MB
Format:
Adobe Portable Document Format
Description:
Published version