Linked Life Data

21216975

Source:http://linkedlifedata.com/resource/pubmed/id/21216975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-2
pubmed:abstractText
We noted a marked increase in IFN? mRNA in newborn (NB) murine lungs after exposure to hyperoxia. We sought to evaluate the role of IFN? in lung injury in newborns. Using a unique triple-transgenic (TTG), IFN?-overexpressing, lung-targeted, externally regulatable NB murine model, we describe a lung phenotype of impaired alveolarization, resembling human bronchopulmonary dysplasia (BPD). IFN?-mediated abnormal lung architecture was associated with increased cell death and the upregulation of cell death pathway mediators caspases 3, 6, 8, and 9, and angiopoietin 2. Moreover, an increase was evident in cathepsins B, H, K, L, and S, and in matrix metalloproteinases (MMPs) 2, 9, 12, and 14. The IFN?-mediated abnormal lung architecture was found to be MMP9-dependent, as indicated by the rescue of the IFN?-induced pulmonary phenotype and survival during hyperoxia with a concomitant partial deficiency of MMP9. This result was concomitant with a decrease in caspases 3, 6, 8, and 9 and angiopoietin 2, but an increase in the expression of angiopoietin 1. In addition, NB IFN? TTG mice exhibited significantly decreased survival during hyperoxia, compared with littermate controls. Furthermore, as evidence of clinical relevance, we show increased concentrations of the downstream targets of IFN? chemokine (C-X-C motif) ligands (CXCL10 and CXCL11) in baboon and human lungs with BPD. IFN? and its downstream targets may contribute significantly to the final common pathway of hyperoxia-induced injury in the developing lung and in human BPD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1535-4989
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
621-30
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A role for matrix metalloproteinase 9 in IFN?-mediated injury in developing lungs: relevance to bronchopulmonary dysplasia.
pubmed:affiliation
Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural