Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/microg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/microg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/microg, 95% CI; 0.08 to 1.72 versus 2.97 pg/microg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/microg, 95% CI; 0.74 to 3.92 versus 4.62 pg/microg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.

The time course of the development of airway hyperresponsiveness (AHR) to inhaled acetylcholine (ACh) and the associated inflammatory cell recovery in bronchoalveolar lavage fluid (BAL) in actively sensitised Brown-Norway rats was studied following challenge with inhaled ovalbumin (OA). IgE for OA was detected in serum obtained from sensitised rats using passive cutaneous anaphylaxis, at titres of 1:10 to 1:30; none was detected in unsensitised animals. There was no significant change in either airway responsiveness to inhaled ACh or in BAL cell counts in rats challenged with saline over the 24 h. Following challenge with a 1% OA aerosol, airway responsiveness to inhaled ACh increased over the 24-hour period, maximal at 18–24 h (saline-challenged group mean ––log PC₂₀₀ 1.95 ± 0.07 M; OA-challenged group mean –log PC₂₀₀ 2.30 ± 0.05 M; p < 0.01). The composition of the inflammatory cells in the BAL fluid after allergen inhalation varied over the 24-hour period, with an initial neutrophilia at 5––8 h (p < 0.01), followed at 18–24 h by an increase in lymphocytes (p < 0.01) and marked eosinophilia (p < 0.01). There was a significant correlation between airway responsiveness and eosinophil recovery at 5–8 h (p < 0.05), and at 18-24 h after allergen exposure (p < 0.05). At 18–24 h there was also a significant correlation between neutrophils and airway responsiveness (p < 0.05). There was no difference between baseline lung resistance in matched saline- or OA-challenged animals at each time point. This animal model may be useful to study the cells and mediators involved in the development of allergen-induced AHR.

Diesel vehicle emissions are the major source of genotoxic compounds in ambient air from urban areas. These pollutants are linked to risks of cardiovascular diseases, lung cancer, respiratory infections and adverse neurological effects. Biological events associated with exposure to some air pollutants are widely unknown but applying omics techniques may help to identify the molecular processes that link exposure to disease risk. Most data on health risks are related to long-term exposure, so the aim of this study is to investigate the impact of short-term exposure (two hours) to air pollutants on the blood transcriptome and microRNA expression levels. We analyzed transcriptomics and microRNA expression using microarray technology on blood samples from volunteers participating in studies in London, the Oxford Street cohort, and, in Barcelona, the TAPAS cohort. Personal exposure levels measurements of particulate matter (PM10, PM2.5), ultrafine particles (UFPC), nitrogen oxides (NO2, NO and NOx), black carbon (BC) and carbon oxides (CO and CO2) were registered for each volunteer. Associations between air pollutant levels and gene/microRNA expression were evaluated using multivariate normal models (MVN). MVN-models identified compound-specific expression of blood cell genes and microRNAs associated with air pollution despite the low exposure levels, the short exposure periods and the relatively smallsized cohorts. Hsa-miR-197-3p, hsa-miR-29a-3p, hsa-miR-15a-5p, hsa-miR-16-5p and hsa-miR-92a-3p are found significantly expressed in association with exposures. These microRNAs target also relevant transcripts, indicating their potential relevance in the research of omics-biomarkers responding to air pollution. Furthermore, these microRNAs are also known to be associated with diseases previously linked to air pollution exposure including several cancers such lung cancer and Alzheimer's disease. In conclusion, we identified in this study promising compound-specific mRNA and microRNA biomarkers after two hours of exposure to low levels of air pollutants during two hours that suggest increased cancer risks.

No abstract

No abstract

cell adhesion, which is currently being further investigated along with effects on integrin signaling pathways. Levels of EMT markers were assessed in MMP12 knockdown and LMO7 overexpressing cells using qPCR, western blotting and immunostaining. Results indicate that higher MMP12 expression is associated with a mesenchymal phenotype, whereas higher LMO7 expression is associated with an epithelial phenotype. Conclusion: Our results suggest that MMP12 is a key driver of migration and invasion in SqCC and its high expression may contribute to EMT, whereas LMO7 is a putative tumor suppressor with a crucial role in maintaining epithelial cell architecture. MMP12 and LMO7 may be potential therapeutic markers for lung cancer at an early stage.

No abstract

Background: Environmental pollutants such as ozone may interact with airway responses to allergen in sensitised individuals. Methods: We examined the effects of a single exposure to ozone (1 ppm for 1 h) on bronchial responsiveness to acetylcholine (ACh) aerosol 3 and 24 h after single ovalbumin (OA) challenge in OA-sensitised anaesthetised guinea pigs. Broncho-alveolar lavage (BAL) was performed and protein content and differential cell counts were determined. Results: Ozone increased bronchial responsiveness at 3 h but not at 24 h, while OA alone had no effect. At 3 h after ozone, OA induced further, but non-significant increases in bronchial responsiveness to ACh, but at 24 h after ozone, there was enhanced responsiveness. Neutrophil counts in BAL fluid increased at 3 and 24 h after exposure to ozone alone, but there were no further increases with ozone followed by OA exposure. Protein concentration was significantly increased in the ozone and OA groups at 3 and 24 h (163.4 ± 25.6 and 128.7 ± 7.4 mg/ml, respectively) compared to 54.0 ± 18.1 mg/ml in the control group (p < 0.02 and p < 0.01, respectively). Conclusion: Our data demonstrate an interaction of OA with ozone exposure on bronchial responsiveness; one underlying mechanism could be through damage at the endothelial-epithelial barrier.