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

O desafio teórico-prático da gestão dos serviços de saúde El desafío teórico práctico de la gestión de los servicios de salud Health services management challenges in theory and practice

Trata-se da temática da gestão de serviços e organizações de saúde, focando os saberes como recurso de ação que se revertem em fontes de autonomia, autoridade e poder dos sujeitos nos contextos de suas práticas. O movimento de consolidação do SUS coloca como desafio a "adequação" dos trabalhadores de saúde aos seus princípios e diretrizes, estabelecendo instrumentos como a gerência de serviços, para a reorganização do processo de trabalho em saúde. Na gestão hospitalar tomou-se o conceito de "ambiência" para compreender e reorganizar a funcionalidade do hospital dando destaque ao espaço físico e tecnológico, considerando que esses elementos não se conformam sem a mediância do social e do afetual.<br>Este artículo se trata de la temática de gestión de servicios y organizaciones de salud, enfocando los saberes como recursos de acción que revierten a fuentes de autonomía, autoridad y poder de los sujetos en los contextos de sus prácticas. El movimiento de consolidación del Sistema Único de Salud (SUS) pone como desafío la "adecuación" de los trabajadores de salud a sus principios y directrices, estableciendo instrumentos tales como la gerencia de servicios, con vistas a la reorganización del proceso de trabajo en salud. En la gestión hospitalaria, se tomó el concepto de "ambiencia" para comprender y reorganizar la funcionalidad del hospital, destacando el espacio físico y tecnológico y considerando que esos elementos no se conforman sin el intermedio del social y del afectual.<br>This article deals with the management of health services and organizations, focusing on knowledge as an action resource, which turns into a source of autonomy, authority and power for subjects in the context of their practices. The movement towards the consolidation of the Single Health System (SUS) gives rise to the challenge of "adapting" health workers to its principles and guidelines, establishing instruments such as service management with a view to the reorganization of the health work process. In hospital management, the concept of "ambience" was adopted to understand and reorganize hospital functionality, highlighting the physical and technological space, in view of the fact that these elements cannot be constituted without the intermedation of the social and affectual