Genetic variance is associated with susceptibility for cigarette smoke-induced DAMP release in mice.
Pouwels, SD
Faiz, A
den Boef, LE
Gras, R
van den Berge, M
Boezen, HM
Korstanje, R
Ten Hacken, NHT
van Oosterhout, AJM
Heijink, IH
Nawijn, MC
- Publisher:
- American Physiological Society
- Publication Type:
- Journal Article
- Citation:
- American Journal of Physiology: Lung Cellular and Molecular Physiology, 2017, 313, (3), pp. L559-L580
- Issue Date:
- 2017-09-01
Closed Access
Filename | Description | Size | |||
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ajplung.00466.2016.pdf | 4.24 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Pouwels, SD | |
dc.contributor.author |
Faiz, A |
|
dc.contributor.author | den Boef, LE | |
dc.contributor.author | Gras, R | |
dc.contributor.author | van den Berge, M | |
dc.contributor.author | Boezen, HM | |
dc.contributor.author | Korstanje, R | |
dc.contributor.author | Ten Hacken, NHT | |
dc.contributor.author | van Oosterhout, AJM | |
dc.contributor.author | Heijink, IH | |
dc.contributor.author | Nawijn, MC | |
dc.date.accessioned | 2022-08-15T04:13:39Z | |
dc.date.available | 2017-05-31 | |
dc.date.available | 2022-08-15T04:13:39Z | |
dc.date.issued | 2017-09-01 | |
dc.identifier.citation | American Journal of Physiology: Lung Cellular and Molecular Physiology, 2017, 313, (3), pp. L559-L580 | |
dc.identifier.issn | 1040-0605 | |
dc.identifier.issn | 1522-1504 | |
dc.identifier.uri | http://hdl.handle.net/10453/160197 | |
dc.description.abstract | Chronic obstructive pulmonary disease (COPD) is characterized by unresolved neutrophilic airway inflammation and is caused by chronic exposure to toxic gases, such as cigarette smoke (CS), in genetically susceptible individuals. Recent data indicate a role for damage-associated molecular patterns (DAMPs) in COPD. Here, we investigated the genetics of CS-induced DAMP release in 28 inbred mouse strains. Subsequently, in lung tissue from a subset of strains, the expression of the identified candidate genes was analyzed. We tested whether small interfering RNA-dependent knockdown of candidate genes altered the susceptibility of the human A549 cell line to CS-induced cell death and DAMP release. Furthermore, we tested whether these genes were differentially regulated by CS exposure in bronchial brushings obtained from individuals with a family history indicative of either the presence or absence of susceptibility for COPD. We observed that, of the four DAMPs tested, double-stranded DNA (dsDNA) showed the highest correlation with neutrophilic airway inflammation. Genetic analyses identified 11 candidate genes governing either CS-induced or basal dsDNA release in mice. Two candidate genes (Elac2 and Ppt1) showed differential expression in lung tissue on CS exposure between susceptible and nonsusceptible mouse strains. Knockdown of ELAC2 and PPT1 in A549 cells altered susceptibility to CS extract-induced cell death and DAMP release. In bronchial brushings, CS-induced expression of ENOX1 and ARGHGEF11 was significantly different between individuals susceptible or nonsusceptible for COPD. Our study shows that genetic variance in a mouse model is associated with CS-induced DAMP release, and that this might contribute to susceptibility for COPD. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | American Physiological Society | |
dc.relation.ispartof | American Journal of Physiology: Lung Cellular and Molecular Physiology | |
dc.relation.isbasedon | 10.1152/ajplung.00466.2016 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0606 Physiology, 1116 Medical Physiology | |
dc.subject.classification | Respiratory System | |
dc.subject.mesh | Alarmins | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Bronchoalveolar Lavage Fluid | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Down-Regulation | |
dc.subject.mesh | Epithelium | |
dc.subject.mesh | Female | |
dc.subject.mesh | Genetic Association Studies | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Genetic Variation | |
dc.subject.mesh | Haplotypes | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Leukocyte Count | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.subject.mesh | Smoking | |
dc.subject.mesh | Alarmins | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Bronchoalveolar Lavage Fluid | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Down-Regulation | |
dc.subject.mesh | Epithelium | |
dc.subject.mesh | Female | |
dc.subject.mesh | Genetic Association Studies | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Genetic Variation | |
dc.subject.mesh | Haplotypes | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Leukocyte Count | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.subject.mesh | Smoking | |
dc.subject.mesh | Epithelium | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Bronchoalveolar Lavage Fluid | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Pulmonary Disease, Chronic Obstructive | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Leukocyte Count | |
dc.subject.mesh | Smoking | |
dc.subject.mesh | Down-Regulation | |
dc.subject.mesh | Haplotypes | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Female | |
dc.subject.mesh | Genetic Variation | |
dc.subject.mesh | Genetic Association Studies | |
dc.subject.mesh | Alarmins | |
dc.title | Genetic variance is associated with susceptibility for cigarette smoke-induced DAMP release in mice. | |
dc.type | Journal Article | |
utslib.citation.volume | 313 | |
utslib.location.activity | United States | |
utslib.for | 0606 Physiology | |
utslib.for | 1116 Medical Physiology | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Centre for Health Technologies (CHT) | |
utslib.copyright.status | closed_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2022-08-15T04:13:36Z | |
pubs.issue | 3 | |
pubs.publication-status | Published | |
pubs.volume | 313 | |
utslib.citation.issue | 3 |
Abstract:
Chronic obstructive pulmonary disease (COPD) is characterized by unresolved neutrophilic airway inflammation and is caused by chronic exposure to toxic gases, such as cigarette smoke (CS), in genetically susceptible individuals. Recent data indicate a role for damage-associated molecular patterns (DAMPs) in COPD. Here, we investigated the genetics of CS-induced DAMP release in 28 inbred mouse strains. Subsequently, in lung tissue from a subset of strains, the expression of the identified candidate genes was analyzed. We tested whether small interfering RNA-dependent knockdown of candidate genes altered the susceptibility of the human A549 cell line to CS-induced cell death and DAMP release. Furthermore, we tested whether these genes were differentially regulated by CS exposure in bronchial brushings obtained from individuals with a family history indicative of either the presence or absence of susceptibility for COPD. We observed that, of the four DAMPs tested, double-stranded DNA (dsDNA) showed the highest correlation with neutrophilic airway inflammation. Genetic analyses identified 11 candidate genes governing either CS-induced or basal dsDNA release in mice. Two candidate genes (Elac2 and Ppt1) showed differential expression in lung tissue on CS exposure between susceptible and nonsusceptible mouse strains. Knockdown of ELAC2 and PPT1 in A549 cells altered susceptibility to CS extract-induced cell death and DAMP release. In bronchial brushings, CS-induced expression of ENOX1 and ARGHGEF11 was significantly different between individuals susceptible or nonsusceptible for COPD. Our study shows that genetic variance in a mouse model is associated with CS-induced DAMP release, and that this might contribute to susceptibility for COPD.
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