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Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [THP1]

ABSTRACT: Background: Monocytes play a crucial role in innate immune responses for host defense, yet their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lung of COPD patients. Methods: Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes from peripheral blood of patients with COPD was also examined. CD45+CD206–CD14+IL-6Rhi and CD45+CD206–CD14+IL-6R– cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate IL-6 responsiveness of IL-6R+ monocytes. Results: The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, while CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced gene expression changes linked to chemotaxis and organism development. Conclusion: In patients with COPD, CD14+IL-6Rhi monocytes increase in lung tissues compared to CNS and exhibit a different transcriptome profile from CD14+IL-6R– monocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265855 | GEO | 2024/08/21

REPOSITORIES: GEO

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Project description:Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease. Objectives: Among inflammatory cell types, alveolar macrophages appear to have a key role in initiating and/or sustaining disease progression. These cells are derived from peripheral monocytes. Identification of disease and cell type specific gene expression profiles can be revealing and also practically useful in order to diagnose and characterize disease progression and the effect of drug treatment. Methods: We used Affymetrix microarrays to obtain gene expression data of alveolar macrophages and circulating monocytes of COPD and healthy control patients. The microarray results were confirmed by quantitative real-time polymerase chain reaction in multiple patient collections. Measurements and Main Results: We have identified gene sets specifically associated with COPD in alveolar macrophages and also in monocytes. Immune function, responses to stimuli, and cell death related genes appear to be impacted in both cell types. Remarkably, there is an overlapping gene set between the two cell types. Conclusions: Taken together, our data show that COPD-specific gene signatures can be identified and validated, and that the disease also affects peripheral monocytes. Moreover, monocytes and alveolar macrophages carry overlapping gene expression signatures. Our findings further support the notion that altered responsiveness to stimuli is the key characteristic of alveolar macrophages and also of their precursors, peripheral monocytes. Brochoalveolar lavage fluid samples were collected from of COPD and healthy control patients. Alveolar macrophages were isolated using Percoll gradient centrifugation, isolated using CD14+ magnetic beads, and total RNA was extracted using Qiagen RNeasy Kit. The monocyte samples represent a pool of RNA from 5 patients. Total RNA was labeled with biotin and individual samples were hybridized to Affymetrix HG U133A GeneChips. Affymetrix data files were analyzed using GeneSpring 7.3 software. Using a non-parametric statistical test, we compared the gene expression patterns of the COPD and the healthy control patients and identified a set a genes that showed differential expression between the two groups.

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Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [THP1]

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