32 research outputs found
Diesel Exhaust Particle-Treated Human Bronchial Epithelial Cells Upregulate Jagged-1 and OX40 Ligand in Myeloid Dendritic Cells via Thymic Stromal Lymphopoietin
Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs
This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Biomarkers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling
MicroRNA-375 Regulation of Thymic Stromal Lymphopoietin by Diesel Exhaust Particles and Ambient Particulate Matter in Human Bronchial Epithelial Cells
Proteomic analysis of mesenchymal stromal cell-derived extracellular vesicles and reconstructed membrane particles
Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) are a potential therapy for immunological and degenerative diseases. However, large-scale production of EV free from contamination by soluble proteins is a major challenge. The generation of particles from isolated membranes of MSC, membrane particles (MP), may be an alternative to EV. In the present study we generated MP from the membranes of lysed MSC after removal of the nuclei. The yield of MP per MSC was 1 × 105 times higher than EV derived from the same number of MSC. To compare the proteome of MP and EV, proteomic analysis of MP and EV was performed. MP contained over 20 times more proteins than EV. The proteins present in MP evidenced a multi-organelle origin of MP. The projected function of the proteins in EV and MP was very different. Whilst proteins in EV mainly play a role in extracellular matrix organization, proteins in MP were interconnected in diverse molecular pathways, including protein synthesis and degradation pathways and demon-strated enzymatic activity. Treatment of MSC with IFNγ led to a profound effect on the protein make up of EV and MP, demonstrating the possibility to modify the phenotype of EV and MP through modification of parent MSC. These results demonstrate that MP are an attractive alternative to EV for the development of potential therapies. Functional studies will have to demonstrate therapeutic efficacy of MP in preclinical disease models
Markers of Th17 inflammation in the lungs.
<p>Groups of wild type or B cell KO mice challenged with saline or OVA-PM were analyzed. Groups of OVA-PM challenged B cell KO mice were either controls [injected with control antibody (open circles) or given no injections (filled circles)] or injected with anti-OVA IgG1 antibody. <b>(A)</b> Legend. <b>(B-E)</b> Bar graphs show mean ± SEM and individual data points for <b>(B)</b> numbers of BAL neutrophils; <b>(C)</b> S100a8; <b>(D)</b> S100a9; and <b>(E)</b> IL-6 gene expression. Gene expression in the lungs is shown as fold-increase over the means of the wild type saline group. Pairs of letters above the bars indicate the pairs of groups that showed significant differences (p<0.05) calculated with the Mann Whitney U test or the t-test with Welch’s correction (unpaired, two-tailed tests). Numbers below the bars indicate the numbers of mice per group.</p
IL-13 & IL-17A response to exposure with OVA-PM<sub>2.5</sub> in wild type and B cell KO mice.
<p>Lymph node and lung tissues from groups of wild type or B cell KO mice challenged with saline or OVA-PM were analyzed. Groups of OVA-PM challenged B cell KO mice were either controls [injected with control antibody (open circles) or given no injections (filled circles)] or injected with anti-OVA IgG1 antibody. <b>(A)</b> Legend. <b>(B)</b> Representative dot plots were generated by flow cytometry of CD4+ T cells (CD3-CD4-dual-positive) showing staining for IL-13 vs. IL-17A. <b>(C-E)</b> The flow cytometry data were numerically analyzed to calculate the numbers for each cell type (mean ± SEM) per lung draining lymph node. <b>(F-H)</b> Gene expression in the lungs of IL-13, IL-17A, IL-17F is indicated (mean ± SEM) as fold-increase over the means of the wild type saline group. Pairs of letters above the bars indicate the pairs of groups that showed significant differences (p<0.05) calculated with the Mann Whitney U test or the t-test with Welch’s correction (unpaired, two-tailed tests). Numbers below the bars indicate the numbers of mice per group.</p
Experimental Design.
<p>Schematic representation of the timing of sensitization by intraperitoneal injection of OVA-Alum; intranasal administration of saline or antigen and PM<sub>2.5</sub> (OVA & PM<sub>2.5</sub>); and the antibody injections administered intraperitoneally.</p
Right ventricular (RV) weight and RV-gene expression.
<p>Groups of wild type and B cell KO mice challenged with saline or OVA-PM were analyzed. Groups of OVA-PM challenged B cell KO mice were either controls [injected with control antibody (open circles) or given no injections (filled circles)] or injected with anti-OVA IgG1 antibody. <b>(A)</b> Legend. <b>(B-G)</b> Bar graphs show mean ± SEM and individual data for right ventricular weight calculated relative to <b>(B)</b> the weight of the left ventricle and septum (RV/LV+S), or <b>(C)</b> body weight (RV/BW); and gene expression in the right ventricle of [BNP <b>(D)</b>, IL-33 <b>(E)</b>, RELMα <b>(F)</b>, RELMγ <b>(G)</b>]. Gene expression in the lungs is shown as fold-increase over the means of the wild type saline group. Pairs of letters above the bars indicate the pairs of groups that showed significant differences (p<0.05) calculated with the Mann Whitney U test (unpaired, two-tailed). Numbers below the bars indicate the numbers of mice per group.</p