			Home About us Contact

Tracheal Epithelial Cells (tracheal + epithelial_cell)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Alcohol Primes the Airway for Increased Interleukin-13 Signaling

ALCOHOLISM, Issue 3 2009
Patrick O. Mitchell
Background:, Using an experimental model of airway fibrosis following lung transplantation, we recently showed that chronic alcohol ingestion by donor rats amplifies airway fibrosis in the recipient. Associated with alcohol-mediated amplification of airway fibrosis is increased transforming growth factor ,-1(TGF,1) and ,-smooth muscle actin expression. Other studies have shown that interleukin-13 (IL-13) modulates TGF,1 signaling during experimentally-induced airway fibrosis. Therefore, we hypothesized that IL-13 is a component of alcohol-mediated amplification of pro-fibrotic mediators in the alcoholic lung. Methods:, To test this hypothesis, we analyzed tracheal epithelial cells and type II alveolar cells from control- or alcohol-fed rats, alcohol-treated mouse lung fibroblasts, and human bronchial epithelial cells in vitro for expression of various components of the IL-13 signaling pathway. Signaling via the IL-13 pathway was assessed by measuring levels of phosphorylated signal transducers and activators of transcription-6 (STAT6). In addition, we performed heterotopic tracheal transplantation using control-fed and alcohol-fed donor rats and analyzed tracheal allografts for expression of components of the IL-13 signaling pathway by RT-PCR and immunocytochemical analyses. Results:, Interleukin-13 expression was detected in type II alveolar epithelial cells and human bronchial epithelial cells, but not in lung fibroblasts. IL-13 expression was decreased in whole lung and type II cells in response to alcohol exposure. In all cell types analyzed, expression of IL-13 signaling receptor (IL-13R,1) mRNA was markedly increased. In contrast, mRNA and protein expression of the IL-13 decoy receptor (IL-13R,2) were decreased in all cells analyzed. Exposure to alcohol also increased STAT6 phosphorylation in response to IL-13 and lipopolysaccharide. Conclusions:, Data from multiple cell types in the pulmonary system suggest that IL-13 and its receptors play a role in alcohol-mediated activation of pro-fibrotic pathways. Taken together, these data suggest that alcohol primes the airway for increased IL-13 signaling and subsequent tissue remodeling upon injury such as transplantation. [source]

Carbocisteine inhibits oxidant-induced apoptosis in cultured human airway epithelial cells

RESPIROLOGY, Issue 7 2009
Motoki YOSHIDA
ABSTRACT Background and objective: Increased oxidant levels have been associated with exacerbations of COPD, and L-carbocisteine, a mucolytic agent, reduces the frequency of exacerbations. The mechanisms underlying the inhibitory effects of L-carbocisteine on oxidant-induced COPD exacerbations were examined in an in vitro study of human airway epithelial cells. Methods: In order to examine the antioxidant effects of L-carbocisteine, human tracheal epithelial cells were treated with L-carbocisteine and exposed to hydrogen peroxide (H2O2). Cell apoptosis was assessed using a cell death detection ELISA, and the pathways leading to cell apoptosis were examined by measurement of caspase-3 and caspase-9 by western blot analysis with fluorescent detection. Results: The proportion of apoptotic cells in human tracheal epithelium was increased in a concentration- and time-dependent manner, following exposure to H2O2. Treatment with L-carbocisteine reduced the proportion of apoptotic cells. In contrast, H2O2 did not increase the concentration of LDH in supernatants of epithelial cells. Exposure to H2O2 activated caspase-3 and caspase-9, and L-carbocisteine inhibited the H2O2 -induced activation of these caspases. L-carbocisteine activated Akt phosphorylation, which modulates caspase activation, and the inhibitors of Akt, LY294002 and wortmannin, significantly reversed the inhibitory effects of L-carbocisteine on H2O2 -induced cell apoptosis. Conclusions: These findings suggest that in human airway epithelium, L-carbocisteine may inhibit cell damage induced by H2O2 through the activation of Akt phosphorylation. L-carbocisteine may have antioxidant effects, as well as mucolytic activity, in inflamed airways. [source]

Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal cells infected with RV14

RESPIROLOGY, Issue 2 2008
Daisuke INOUE
Background and objective: The common cold is a major cause of asthma exacerbation and chronic obstructive lung disease. Rhinovirus is reported to be responsible for more than 50% of cases of the common cold. In a previous study, we reported that rhinovirus infection of cultured airway cells induced MUC5AC mucin overproduction and hypersecretion by activating the p44/42 mitogen-activated protein kinase (p44/42 MAPK) pathway. The aim of this study was to examine the effect of erythromycin on RV14-induced airway mucin overproduction and hypersecretion. Methods: RV14-infected human tracheal epithelial cells were treated with erythromycin. Results: Erythromycin blocked RV14-induced MUC5AC protein overproduction and hypersecretion, and also blocked RV14-induced p44/42 MAPK activation in the cells. Conclusions: Erythromycin may attenuate RV14-induced MUC5AC overproduction and hypersecretion by blocking the p44/42 MAPK pathway or its upstream regulators. [source]

Expression and role of Notch signalling in the regeneration of rat tracheal epithelium

CELL PROLIFERATION, Issue 1 2009
X.-B. Ma
Objectives:, This study is to explore the role of Notch signalling during the regeneration of rat tracheal epithelium after injury induced by 5-fluorouracil (5-FU). Materials and methods:, We developed an ex vivo model of rat tracheal epithelial regeneration using 5-FU to induce injury. Expression levels of members of the Notch signalling pathway, ABCG2, CK19, and proliferating cell nuclear antigen (PCNA) were examined by reverse transcription,polymerase chain reaction, Western blot, and immunofluorescence. One group of tracheas were cultured in the medium with a ,-secretase inhibitor or Jag-1 peptide after 5-FU treatment and another group were pre-treated with the ,-secretase inhibitor or Jag-1 peptide before 5-FU treatment. The expression changes of ABCG2, CK19, and PCNA were examined by Western blot or immunofluorescence and the morphologic changes were observed by haematoxylin and eosin stain during the recovery process. Results:, Expression levels of Notch3, Jagged1, and Hey1 were increased in rat tracheal epithelial cells after treatment with 5-FU. During injury recovery, disruption of Notch signalling by treatment with the ,-secretase inhibitor reduced expression of ABCG2 and PCNA, but promoted expression of CK19, while persistent activation of Notch signalling promoted expression of ABCG2 and PCNA, but reduced expression of CK19. Under both conditions, recovery from injury was reduced. However, blocking Notch signalling prior to 5-FU treatment led to the complete blockage of recovery, while activating Notch signalling before 5-FU treatment promoted recovery. Conclusions:, During tracheal epithelial regeneration, Notch signalling maintains an undifferentiated state and promotes proliferation among a population of tracheal epithelial cells. [source]