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- Padra, Médea, 1986, et al.
(author)
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Increased MUC1 plus a larger quantity and complex size for MUC5AC in the peripheral airway lumen of long-term tobacco smokers
- 2020
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In: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 134:10, s. 1107-1125
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Journal article (peer-reviewed)abstract
- There is little information on mucins versus potential regulatory factors in the peripheral airway lumen of long-term smokers with (LTS+) and without (LTS-) chronic obstructive pulmonary disease (COPD). We explored these matters in bronchoalveolar lavage (BAL) samples from two study materials, both including LTS+ and LTS- with a very similar historic exposure to tobacco smoke, and healthy non-smokers (HNSs; n=4-20/group). Utilizing slot blot and immunodetection of processed (filtered and centrifuged), as well as unprocessed BAL samples from one of the materials, we compared the quantity and fraction of large complexes of mucins. All LTS displayed an enhanced (median) level of MUC5AC compared with HNS. LTS- displayed a higher level of large MUC5AC complexes than HNS while LTS+ displayed a similar trend. In all LTS, total MUC5AC correlated with blood leukocytes, BAL neutrophil elastase and net gelatinase activity. Large mucin complexes accounted for most MUC5B, without clear group differences. In all LTS, total MUC5B correlated with total MUC5AC and local bacteria. In the same groups, large MUC5B complexes correlated with serum cotinine. MUC1 was increased and correlated with BAL leukocytes in all LTS whereas MUC2 was very low and without clear group differences. Thus, the main part of MUC5AC and MUC5B is present as large complexes in the peripheral airway lumen and historic as well as current exposure to tobacco smoke emerge as potential regulatory factors, regardless of COPD per se. Bacteria, leukocytes and proteinases also constitute potential regulatory factors, of interest for future therapeutic strategies.
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- Che, K. F., et al.
(author)
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Interleukin-26 in Antibacterial Host Defense of Human Lungs Effects on Neutrophil Mobilization
- 2014
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 190:9, s. 1022-1031
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Journal article (peer-reviewed)abstract
- Rationale: The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known. Objectives: To characterize the role of IL-26 in antibacterial host defense of human lungs. Methods: Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytoldnes and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro. Measurements and Main Results: Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells. Conclusions: This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.
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- Che, K. F., et al.
(author)
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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
- 2018
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In: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 132:9, s. 959-983
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Journal article (peer-reviewed)abstract
- Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor kappa B (NF-kappa B); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-kappa B and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
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