Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke

<p>Abstract</p> <p>Background</p> <p>Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated.</p> <p>Methods</p> <p>Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting.</p> <p>Results</p> <p>Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of <it>interleukin 6 </it>(<it>IL-6</it>) and its antagonist, <it>suppressor of cytokine signalling </it>(<it>SOCS3</it>) mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3), basal cell-lymphoma extra large (BCL-XL) and myeloid cell leukemia 1 (MCL-1) protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure.</p> <p>Conclusion</p> <p>Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS.</p

Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort

<p>Abstract</p> <p>Background</p> <p>Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system.</p> <p>Methods</p> <p>Exposure to background particulate matter less than 10 μm in diameter (PM₁₀) and nitrogen dioxide (NO₂) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets.</p> <p>Results</p> <p>Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 μg/m³increase in PM₁₀levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO₂exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO₂exposure and an increased percentage of CD8+ T-cells.</p> <p>Conclusions</p> <p>These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.</p

Splenic macrophage precursor cells from Leishmania donovani infected mice as cytotoxic effectors against pro- and amastigotes

The most important effectors of natural- as well as lymphokine-mediated cytotoxicity against microbicidal and fungal targets and protozoa such as Leishmania donovani are represented by cells of the monocyte-macrophage lineage. We recently described the bone marrow-derived macrophage precursor which is able to spontaneously and extracellularly kill protozoa of the genus Leishmania. These nonadherent, nonphagocytic macrophage precursor cells are present in the spleen of healthy mice only in a small quantity; however, high nmumbers have been isolated from the spleen of L. donovani infected mice. Macrophage precursors from spleen of diseased animals are able to kill spontaneously the promastigote as well as the amastigote form of L. donovani. the mechanism of the spontaneous leishmanicidal activity of macrophage precursor cells derived from spleens of L. donovani infected mice was investigated. This effector function could be defined in part as an antibody-dependent cellular cytotoxicity ( ADCC). In addition we assessed the role of CSFI containing L-cell donditioned supernatant at the leishmanicidal activity of these immature cells of the macrophage lineage. For that purpose, nonadherent cells from healthy mice were cocultivated with this CSFI containing medium for four days. These in vitro proliferated macrophage precursor cells from untreated mice showed an increased leishmanicidal activity. (-y-

Functional heterogeneity of macrophage precursor cells from spleen of Leishmania donovani-infected and untreated mice

Cells belonging to the monocyte-macrophage lineage are known to be among the most important effectors of natural - as well as lymphokine - mediated cytotoxicity against tumor cells, microbial and fungal targets and protozoa. Recent observations (1) pressented evidence that macrophage precursor cells are not confined to the bone marrow compartment, but can also be found in a peripheral organ such as the spleen. Only a very small quantity of these cells is present in the spleens of normal, untreated mice. In contrast, large numbers of splenic macrophage precursors can be isolated from Leishmania donovani-infected C57BL/6 mice in the early stage of infection as well as three months post infectionem. We demonstrate the capability of these highly purified population of nonadherent, nonphagocytic macrophage precursors, derived from spleen parasitized with Leishmania donovani, to spontaneously kill the promastigote form of Leishmania donovani and Leishmania enriettii. These effector functions , however, are not found in healthy control C57BL/6 mice. The functional heterogeneity displayed by splenic macrophage precursors from Leishmania donovani-infected C57BL/6 mice and untreated animals is dicussed