BackgroundThe Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state.Methodology/Principal FindingsMicroarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro.Conclusions/SignificanceSmoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.
It was often uncertain whether antiseptics were associated with any difference in healing, infections, or other outcomes. Where there is moderate or high certainty evidence, decision makers need to consider the applicability of the evidence from the comparison to their patients. Reporting was poor, to the extent that we are not confident that most trials are free from risk of bias.
The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. Based on the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th–12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most striking change was for TLR5, which was down-regulated in healthy smokers (1.4-fold, p<10−10) and smokers with COPD (1.6-fold, p<10−11). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, were highly induced by flagellin in TLR5 high-expressing cells compared to TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.
Concentrations of ambient ozone (O 3 ) and nitrogen oxides (NO x ) were measured continuously for a period of 12 months in the city of Jeddah from December 2011 to December 2012. Meteorological parameters, wind speed, temperature, and relative humidity were also monitored. Concentrations of ground O 3 were found to be highly dependent on the NO x diurnal cycle and wind speed. Nitrogen oxides were found to exceed air quality standards, especially in industrial sites, while O 3 concentrations were found to exceed 40 ppb, averaged over 1 h, on more than 24% of the measured days in the rural sites. Furthermore, they exceeded 30% in all other areas (i.e., the urban ones).O 3 and NO x were inversely related. The highest average NO x concentration (96 ppb) occurred in a rural area downwind of a desalination plant, while the average O 3 concentration peaked in a rural area upwind of a desalination plant, reaching 63.5 ppb, although it also reached 72.6 in another rural area, and we consider this latter result as the background figure in the present study. The seasonal variations of O 3 were more distinct than those of NO x . To the best of our knowledge, this is the first report providing comprehensive background information on air quality in an arid area of the developing world.
SUMMARYThe effects of ()., (80 nl I"') on the photosynthetic rate (A) and stomatal conductance (gj of Egyptian varieties of radish [Raplianus sativus L, cv, Baladey) and turnip (Brassica rapa L, c\ , Sultani) were examined. Exposure to Od ecreased A in both species, while g. was increased in radish and decreased in turnip. The effect of different concentrations of C, (50, 100, 150 nl 1"') on radish was examined and it was found that A decreased, while gî ncreased, with increasing concentrations of O^j.Scanning electron microscopy (SEM) of fumigated leaves showed that the increase in g^ in radish resulted from the collapse of epidermal cells. Counts of the percentage of stomata which were fully open demonstrated that 80 nl r^ O^ caused an increase of 18 "o in radish and a decrease of 14 "u in turnip. The proportion of opened stomata was found to increase with increasing O^ concentration in radish.
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