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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 01, 2007 |
| Title |
Expression data from mouse lung with recombinant human soluble PBEFtreatment and ventilator-induced lung injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI.
Keywords: We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI.
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| Overall design |
animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.
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| Contributor(s) |
Hong SA, Huang Y, Sammani S, Moreno-Vinasco L, Lussier YA, Garcia JG |
| Citation(s) |
18658108 |
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| Submission date |
Oct 12, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Yong Huang |
| E-mail(s) |
yh9fj@virginia.edu
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| Phone |
(434) 243-0842
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| Organization name |
University of Viginia
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| Department |
Medicine
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| Street address |
1340 Jefferson Park Ave
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA102973 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9314_RAW.tar |
55.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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