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1.
Front Immunol ; 15: 1346491, 2024.
Article in English | MEDLINE | ID: mdl-38911863

ABSTRACT

Introduction: Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1ß, IL-6, IL-8, TNF-α). Methods: Mouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts. Results: EC exposure increased the number and size of organoids formed, and upregulated Lamp3, Muc5ac and Muc5b expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of Il33, Tgfa and Areg was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated Foxj1 expression and upregulated Aqp5 expression in day 14 organoids. Conclusions: EC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.


Subject(s)
Epithelial Cells , Fibroblasts , Organoids , Pulmonary Disease, Chronic Obstructive , Animals , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/immunology , Humans , Mice , Fibroblasts/metabolism , Epithelial Cells/metabolism , Cytokines/metabolism , Lung/pathology , Lung/immunology , Lung/metabolism , Cells, Cultured , Disease Progression , Respiratory Mucosa/metabolism , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Mice, Inbred C57BL
2.
Pharmaceutics ; 14(2)2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35214052

ABSTRACT

Swallowing problems and the required dose adaptations needed to obtain optimal pharmacotherapy may be a hurdle in the use of tablets in daily clinical practice. Tablet splitting, crushing, or grinding is often applied to personalise medication, especially for the elderly and children. In this study, the performance of different types of (commercially available) devices was studied. Included were splitters, screwcap crushers, manual grinders, and electric grinders. Unscored tablets without active ingredient were prepared, with a diameter of 9 and 13 mm and a hardness of 100-220 N. Tablets were split into two parts and the difference in weight was measured. The time needed to pulverise the tablets (crush time) was recorded. The residue remaining in the device (loss) was measured. The powder was sieved to obtain a particle fraction >600 µm and <600 µm. The median particle size and particle size distribution of the later fraction were determined using laser diffraction analysis. Splitting tablets into two equal parts appeared to be difficult with the devices tested. Most screwcap grinders yielded a coarse powder containing larger chunks. Manual and especially electric grinders produced a finer powder, making it suitable for administration via an enteral feeding tube as well as for use in individualised preparations such as capsules. In conclusion, for domestic and incidental use, a screwcap crusher may provide sufficient size reduction, while for the more demanding regular use in hospitals and nursing residences, a manual or electric grinder is preferred.

3.
Trends Pharmacol Sci ; 42(5): 354-366, 2021 05.
Article in English | MEDLINE | ID: mdl-33612289

ABSTRACT

Interleukin (IL)-11 was originally recognized as an immunomodulatory and hematopoiesis-inducing cytokine. However, although IL-11 is typically not found in healthy individuals, it is now becoming evident that IL-11 may play a role in diverse pulmonary conditions, including IPF, asthma, and lung cancer. Additionally, experimental strategies targeting IL-11, such as humanized antibodies, have recently been developed, revealing the therapeutic potential of IL-11. Thus, further insight into the underlying mechanisms of IL-11 in lung disease may lead to the ability to interfere with pathological conditions that have a clear need for disease-modifying treatments, such as IPF. In this review, we outline the effects, expression, signaling, and crosstalk of IL-11 and focus on its role in lung disease and its potential as a therapeutic target.


Subject(s)
Asthma , Interleukin-11 , Lung Diseases , Lung Neoplasms , Asthma/drug therapy , Humans , Interleukin-11/immunology , Lung , Lung Diseases/drug therapy , Signal Transduction
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