Respiratory epithelium

About: Respiratory epithelium is a research topic. Over the lifetime, 5048 publications have been published within this topic receiving 222304 citations. The topic is also known as: respiratory tract epithelium & Respiratory Mucosa.

Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma

Abstract: Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

Tissue factor–bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo

Abstract: Background Tissue factor (TF), a primary initiator of blood coagulation, also plays a pivotal role in angiogenesis. TF expression in the airways is associated with asthma, a disease characterized in part by subepithelial angiogenesis. Objectives To determine potential sources of TF and the mechanisms of its availability in the lung microenvironment. Methods Normal human bronchial epithelial cells grown in air-liquid interface culture were subjected to a compressive stress of 30 cm H 2 O; this is comparable to that generated in the airway epithelium during bronchoconstriction in asthma. Conditioned media and cells were harvested to measure TF mRNA and TF protein. We also tested bronchoalveolar lavage fluid and airway biopsies from asthmatic patients and healthy controls for TF. Results TF mRNA was upregulated 2.2-fold after 3 hours of stress compared with unstressed cells. Intracellular and secreted TF proteins were enhanced 1.6-fold and more than 50-fold, respectively, compared with those of control cells after the onset of compression. The amount of TF in the bronchoalveolar lavage fluid from patients with asthma was found at mean concentrations that were 5 times greater than those of healthy controls. Immunohistochemical staining of endobronchial biopsies identified epithelial localization of TF with increased expression in asthma. Exosomes isolated from the conditioned media of normal human bronchial epithelial cells and the bronchoalveolar lavage fluid of asthmatic subjects by ultracentrifugation contained TF. Conclusions Our in vitro and in vivo studies show that mechanically stressed bronchial epithelial cells are a source of secreted TF and that exosomes are potentially a key carrier of the TF signal.

Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation.

Abstract: Using adenoviral-mediated gene transfer techniques, the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene is efficiently targeted to and highly expressed by the respiratory epithelium of rat lung. This lung tissue-directed expression of GM-CSF induces accumulation of both eosinophils and macrophages at early stages and an irreversible fibrotic reaction at later stages. These tissue responses to GM-CSF appear to be distinct from those induced by other proinflammatory cytokines, interleukin (IL)-5, IL-6, macrophage inflammatory protein-2 (MIP-2), or RANTES overexpressed in the lung. These findings clearly demonstrate that GM-CSF is more than a hematopoietic cytokine in the lung and may play a pivotal role in the multiple pathological processes underlying numerous respiratory illnesses, including asthma. In this overview, the differences in tissue responses induced by GM-CSF and other individual cytokines are highlighted. In addition, the mechanisms by which GM-CSF and other individual cytokines are highlighted. In addition, the mechanisms by which GM-CSF contributes to the development of eosinophilia, macrophage granuloma, and fibrosis are discussed in conjunction with the recent findings from us and others.

Conditional deletion of Nrf2 in airway epithelium exacerbates acute lung injury and impairs the resolution of inflammation

Abstract: Oxidant stress, resulting from an excess of reactive electrophiles produced in the lung by both resident (epithelial and endothelial) and infiltrated leukocytes, is thought to play an obligatory role in tissue injury and abnormal repair. Previously, using a conventional (whole-body) knockout model, we showed that antioxidative gene induction regulated by the transcription factor Nrf2 is critical for mitigating oxidant-induced (hyperoxic) stress, as well as for preventing and resolving tissue injury and inflammation in vivo. However, the contribution to pathogenic acute lung injury (ALI) of the cellular stress produced by resident versus infiltrated leukocytes remains largely undefined in vivo. To address this critical gap in our knowledge, we generated mice with a conditional deletion of Nrf2 specifically in Clara cells, subjected these mice to hyperoxic insult, and allowed them to recover. We report that a deficiency of Nrf2 in airway epithelia alone is sufficient to contribute to the development and progression of ALI. When exposed to hyperoxia, mice lacking Nrf2 in Clara cells showed exacerbated lung injury, accompanied by greater levels of cell death and epithelial sloughing than in their wild-type littermates. In addition, we found that an Nrf2 deficiency in Clara cells is associated with a persistent inflammatory response and epithelial sloughing in the lungs during recovery from sublethal hyperoxic insult. Our results demonstrate (for the first time, to the best of our knowledge) that Nrf2 signaling in Clara cells is critical for conferring protection from hyperoxic lung injury and for resolving inflammation during the repair process.

Toll-8/Tollo Negatively Regulates Antimicrobial Response in the Drosophila Respiratory Epithelium

Abstract: Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP) production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spatzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM). Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium.