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.

Airborne particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors

Abstract: PM10, the commonly used indicator of respirable environmental suspended particulate matter with a mean aerodynamic diameter of less than 10 microm, is composed of organic or elemental carbon aggregates containing various metals, acid salts, organic pollutants (polyaromatic hydrocarbons, quinones, nitroaromatic hydrocarbons, etc.), and biological contaminants. In urban and industrial areas, fossil fuel combustion products (e.g., diesel exhaust particles and residual oil fly ash) are the main contributors to PM10. Epidemiological data show that air pollution particulates cause adverse pulmonary health effects, especially in individuals with preexisting lung diseases. A critical cell type that encounters particles after inhalation and that is affected in a number of respiratory diseases is the epithelial cell of the airway and alveoli. In vitro studies have shown that PM10 is responsible for the production and the release of inflammatory cytokines by the respiratory tract epithelium as well as for the activation of the transcription factor NFkappaB. As many of the adsorbed materials on the particle surface are direct oxidants (metals, quinones) and indirectly produce reactive oxygen species, it is hypothesized that oxidative stress may be a component of the mechanisms by which particles activate cytokine production and NFkappaB in epithelial cells.

c-fos proto-oncogene expression in bronchial biopsies of asthmatics.

Abstract: c-fos, a proto-oncogene regulating the transcription of many genes, plays a critical role in the cell cycle and differentiation and may be involved in the regulation of inflammation in asthma. Very low levels of c-fos are detectable in most human cells, and its expression is rapidly and transiently increased by multiple factors, some of which are involved in the airways inflammation of asthma (histamine, eicosanoids, and cytokines). The presence of c-fos protein, as detected by immunofluorescence, and the immunoreactivity of PCNA, a cell proliferation marker, were examined in bronchial biopsies obtained from 12 asthmatics and 10 normal subjects. Biopsies of eight of 12 asthmatics expressed c-fos versus none of 10 normal subjects. The expression was heterogeneous and localized to cells positive for anti-cytokeratin monoclonal antibody, indicating their epithelial origin. On the other hand, PCNA immunoreactivity was only observed in one asthmatic and one control subject but it was not related with c-fos expression. This study demonstrates the induction of c-fos in epithelial cells of asthmatics, suggesting a role for this proto-oncogene in activation rather than in proliferation.

Gene transfer by guanidinium-cholesterol cationic lipids into airway epithelial cells in vitro and in vivo

Abstract: Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis(guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system.

Th17 Cells in Airway Diseases

Abstract: Chronic inflammation is a key feature of many airway diseases. Leukocyte accumulation in the lung has the capacity to mediate many aspects of the pathophysiology of such diseases including asthma and chronic obstructive pulmonary disease (COPD). Until recently, the CD4+ lymphocyte component of these inflammatory influxes was thought to consist of Th1 or Th2 type cells, however a third group of cells termed Th17 have been identified. These cells follow a distinct differentiation profile requiring TGFbeta and IL-6 leading to the expression of the Th17 selective transcription factor, RORgammat. Differentiation of these cells is restricted by Th1 and Th2 cytokines including IFNgamma and IL-4 which attenuate Th17 cell differentiation. The presence of Th17 cells in the airway has yet to be confirmed, yet IL-17 is expressed in both asthma and COPD. Many of the inflammatory effects of Th17 cells are attributed to the expression of this cytokine. For example, IL-17 up-regulates the expression of a number of CXCR2 chemokines including CXCL1, CXCL6 and CXCL8 together with neutrophil survival factors GM-CSF and G-CSF from the airway epithelium. This would suggest that Th17 cells are important in promoting and sustaining neutrophilic inflammation as observed in severe asthma and COPD. In addition, IL-17 can act synergistically with viral infection or other inflammatory mediators including TNF-alpha to potentiate these responses. Confirmation of the presence of Th17 cells in the airways in disease warrants further investigation since these cells would present a novel therapeutic opportunity to reduce neutrophilic inflammation in the lung.