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Status |
Public on Oct 19, 2011 |
Title |
Protective Role of IL-10 in Ozone-induced Pulmonary Inflammation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying IL-10-mediated attenuation of O3-induced pulmonary inflammation in mice. Methods: Il10-deficient (Il10-/-) and wild type (Il10+/+) mice were exposed to 0.3-ppm O3 or filtered air for 24, 48 or 72 hr. Immediately following exposure, differential cell counts, and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10-/- mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
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Overall design |
PARALLEL study design with 26 samples. Biological replicates: 2 to 3 replicates per group with wild type air exposed animals as controls for each time point (24, 48, 72 hours). Time-Course, Dose-Response, Strain comparison
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Contributor(s) |
Backus GS, Howden R, Fostel J, Bauer AK, Cho H, Marzec J, Peden DB, Kleeberger SR |
Citation(s) |
20826374 |
Submission date |
Nov 03, 2010 |
Last update date |
May 04, 2018 |
Contact name |
Steven R Kleeberger |
E-mail(s) |
kleeber1@niehs.nih.gov
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Organization name |
National Institute of Environmental Health Sciences, NIH
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Lab |
Laboratory of Respiratory Biology
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Street address |
111 TW Alexander Dr., Building 101, MD D-201
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City |
Research Triangle Park |
State/province |
NC |
ZIP/Postal code |
27709 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (26)
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Relations |
BioProject |
PRJNA134415 |
Supplementary file |
Size |
Download |
File type/resource |
GSE25095_RAW.tar |
52.3 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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