The air–liquid interface model

The airway epithelium lining the airways is in first contact with the inhaled environment, which contains allergens, gaseous pollutants, particulates, and pathogenic microorganisms. It forms an ion- and size-selective barrier between the inhaled environment and the underlying tissue by the formation of intercellular tight junctions and adhesion junctions. Additionally, the airway epithelium plays an important role in innate immune defense, expressing receptors that recognize molecular patterns from pathogenic microbes, parasites, fungi, and allergens and danger signals from damaged cells, directing proinflammatory processes. Chronic lung diseases, such as asthma and chronic obstructive pulmonary disease, involve changes in airway epithelial function. For valuable insights into these changes, in vitro models should closely recapitulate human airway epithelial composition, three-dimensional structure, and function as an immunological barrier. The goal of this chapter is to review the literature on the use of air–liquid interface cultures to model the lung epithelium in health and disease.</p

Dynamic differences in dietary polyunsaturated fatty acid metabolism in sputum of COPD patients and controls

Introduction: Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis. Objectives: Here we investigated if PUFA metabolism is disturbed in COPD patients. Methods: Free PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed. Results: Significantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling. Conclusions: Our findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.publishedVersio

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN, CLCA1, and SERPINB2 This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2-high and Th2-low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL-13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin-related genes MUC5AC and SPDEF in air-liquid interface differentiated human bronchial (ALI-PBEC) and tracheal epithelial cells (ALI-PTEC). Cultures were exposed to IL-13 for 14 days followed by 5 days of IL-13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14 days, followed by 5 days CS with IL-13. POSTN, SERPINB2, and CLCA1 expression were measured 24 h after the last exposure to CS and IL-13. In both models POSTN, SERPINB2, and CLCA1 expression were increased by IL-13. CS markedly affected the IL-13-induced Th2 gene signature as indicated by a reduced POSTN, CLCA1, and MUC5AC expression in both models. In contrast, IL-13-induced SERPINB2 expression remained unaffected by CS, whereas SPDEF expression was additively increased. Importantly, cessation of CS exposure failed to restore IL-13-induced POSTN and CLCA1 expression. We show for the first time that CS differentially affects the IL-13-induced gene signature for Th2-high asthma. These findings provide novel insights into the interaction between Th2 inflammation and cigarette smoke that is important for asthma pathogenesis and biomarker-guided therapy in asthma

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Dynamic postural stability differences between male and female players with and without ankle sprain

Objectives: The strategy for dynamic postural stability might be different for male and female players. Additionally, dynamic and challenging tasks are recommended to measure differences in postural stability between injured and non-injured players. Therefore, the dynamic stability index (DSI) was developed which measures the ability of a player to maintain static balance after a dynamic task. The first aim of this study was to evaluate DSI differences between males and females for different jump directions. The second aim was to examine both preseason DSI differences between players with and without a history of ankle sprain, and between players with and without an ankle sprain during the subsequent season.Design: Prospective cohort design. Setting: Laboratory. Participants: 47 male (22.9 ± 3.9 y, 193.5 ± 7.9 cm, 87.1 ± 10.6) and 19 female (21.5 ± 2.9 y, 175.9 ± 7.3 cm, 69.0 ± 11.7 kg) sub-elite and elite basketball, volleyball and korfball players. Main outcome measures: Ankle sprain history was collected using a general injury history questionnaire. DSI on a single-leg hop-stabilization task measured preseason were calculated by using force plates and a Matlab program. Ankle sprains were reported during subsequent season. Results: Male players demonstrated larger DSI than female players on forward medial/lateral stability index (MLSI) (0.037± 0.007 vs 0.029 ± 0.005) and vertical stability index (VSI) (0.369 ± 0.056 vs 0.319 ± 0.034) (p < 0.001), diagonal VSI (0.363 ± 0.046 vs 0.311 ± 0.033) (p < 0.001), and lateral anterior/posterior stability index (APSI) (0.062 ± 0.015 vs 0.047 ± 0.011) and VSI (0.350 ± 0.054 vs 0.294 ± 0.037) (p < 0.001). Forward (0.384 ± 0.055 vs 0.335 ± 0.033), diagonal (0.379 ± 0.046 vs 0.328 ± 0.032) and lateral (0.368 ± 0.053 vs 0.313 ± 0.035) dynamic postural stability indices (DPSI) were larger for males (p < 0.001). No significant differences were found between players with and without a previous ankle sprain nor between players with and without an ankle sprain during subsequent season

Chapter 8 Lung-on-Chip

An increasing collection of cell culture techniques is currently available to model the lung microenvironment and study lung diseases, tissue, and tissue regeneration. In this chapter, developments in the field of organs-on-chips (OOC) are discussed with a specific focus on lung-on-chip. Features of airway and alveolus lung-on-chip models are described separately, with a focus on both the cell biology and bioengineering aspects. These include options to study crosstalk between various cell types and the extracellular matrix and the application of lung-specific mechanical forces that result from air and blood flow as well as stretch induced by breathing. Utilizing human induced pluripotent stem cell technology to generate lung cells for culture on-chip and coupling a lung-on-chip with other OOC increase their potential even further. The use of lung-on-chip models for disease modeling, inhalation toxicology, drug development, and screening is discussed as well as their potential for studying lung repair and regeneration