The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA271381 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1737230.fastq.gz | Fastqsanger.gz | |||
| SRR1737231.fastq.gz | Fastqsanger.gz | |||
| SRR1737232.fastq.gz | Fastqsanger.gz | |||
| SRR1737233.fastq.gz | Fastqsanger.gz | |||
| SRR1737234.fastq.gz | Fastqsanger.gz |
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Project description: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.
2024-06-05 | GSE64593 | GEO
Project description: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.
2024-06-05 | GSE64598 | GEO
Project description:HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke. Keywords: expression study
2016-03-24 | GSE10038 | GEO
Project description:HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke. Keywords: expression study Asymptomatic HIV+ smokers with early emphysema
2016-03-24 | E-GEOD-10038 | biostudies-arrayexpress
Project description:The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers [Affymetrix]
| PRJNA271372 | ENA
Project description:The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers [RNA-seq]
| PRJNA271382 | ENA
Project description:Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1(+) smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1(+) smokers contains increased levels of inflammatory cytokines compared to HIV1(-) smokers, we hypothesized that upregulation of lung cytokines in HIV1(+) smokers may be functionally related to increased MMP-9 expression. Methods. 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. Results. 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 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. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1(+) smokers and suggests that Th17 related inflammation may play a role.
| S-EPMC4942665 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-05 | GSE64599 | GEO
Project description:Comparison of severely emphysematous tissue removed at lung volume reduction surgery to that of normal or mildly emphysematous lung tissue resected from smokers with nodules suspicious for lung cancer. Data obtained from the 18 patients with severe emphysema and 12 patients with mild/no emphysema. Research may provide insights into the pathogenetic mechanisms involved in chronic obstructive pulmonary disease (COPD).
2007-08-13 | E-GEOD-1650 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2015-08-28 | PXD001977 | Pride