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| Status |
Public on Jun 05, 2024 |
| Title |
The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Matrix metalloproteinase-9 (MMP-9) expression is up-regulated in alveolar macrophages (AM) of HIV1+ smokers who develop emphysema. Based on the knowledge that lung epithelial lining fluid (ELF) of HIV1+ smokers has increased levels of inflammatory cytokines compared to HIV1- smokers, we hypothesized up-regulation of lung cytokines in HIV1+ smokers may be functionally related to increased MMP-9 expression. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1‾ healthy nonsmokers, HIV1‾ healthy smokers, HIV1‾ smokers with low diffusing capacity (DLCO) , HIV1 + nonsmokers, and HIV1 + smokers with low DLCO. Among several pro-inflammatory cytokines elevated in ELF associated with smoking and HIV1+, increased levels of the Th17-related cytokine IL-23 were found in HIV1- smokers with low DLCO and HIV1+ smokers and nonsmokers. Relative IL-23 gene expression was significantly increased in AM of HIV1+ individuals, with greater expression in AM of HIV1+ smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. Since AM purified by adherence contain a small number of lymphocytes, we hy-pothesized that in an AM/lymphocyte co-culture system, IL-23 would up-regulate MMP-9. IL-23 stimulation of AM/lymphocyte co-cultures in vitro induced increased MMP-9 mRNA levels and protein. AM of healthy individuals did not express IL-23 receptors (IL-23R), lung T lymphocytes express IL-23R and interact with AM in order to up-regulate MMP-9. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+ smokers and suggests that Th-17 related inflammation may play a role.
IL-23 upregulates MMP-9 expression in human alveolar macrophages via a T lymphocyte/alveolar macrophage interaction, suggesting a possible role for Th-17 related inflammation in accelerated emphysema in HIV1+ smokers.
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| Overall design |
RNAseq-based expression profiling of alveolar macrophages from HIV1- nonsmokers, smokers, and smokers with COPD.
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| Contributor(s) |
Barjaktarevic IZ, Crystal RG, Kaner RJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 31, 2014 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Yael Strulovici-Barel |
| E-mail(s) |
[email protected]
|
| Organization name |
Weill Cornell Medical College
|
| Department |
Department of Genetic Medicine
|
| Lab |
Crystal
|
| Street address |
1300 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE64599 |
The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers |
|
| Relations |
| BioProject |
PRJNA271382 |
| SRA |
SRP051639 |
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