| Autor: |
López-Boado YS; GlaxoSmithKline, King of Prussia, Pennsylvania, USA., Li JU, Clayton CL, Wright JL, Churg A |
| Jazyk: |
angličtina |
| Zdroj: |
Inhalation toxicology [Inhal Toxicol] 2010 Feb; Vol. 22 (3), pp. 234-44. |
| DOI: |
10.3109/08958370903191437 |
| Abstrakt: |
Although a number of animal model studies have addressed changes in gene expression in the parenchyma and their relationship to emphysema, much less is known about the pathogenesis of cigarette smoke-induced small airway remodeling. In this study the authors exposed rat tracheal explants, a model of the airway wall, to whole smoke for 15 min, and then cultured the explants in air. The airway transcriptome was evaluated using RAE 230_2 gene chips. By 2 h after starting smoke exposure, expression levels of 502 genes were differentially expressed by more than 1.5 times (p < .01 or less) and by 24 h 1870 genes were significantly changed up or down. These included genes involved in antioxidant protection, epithelial defense and remodeling, inflammatory mediators and transcription factors, and a number of unexpected genes, including the matrix metalloproteinase (MMP)-12 inducer, tachykinin-1 (substance P). Pretreatment of the explants with 1 x 10(-7) M dexamethasone reduced the number of significantly changed genes by approximately 47% at 2 h and 68% at 24 h and in almost all instances reduced the magnitude of the smoke-induced changes. The authors conclude that even a very brief exposure to cigarette smoke can lead to rapid changes in the expression of a large number of genes in rat tracheal explants, and that these effects are directly mediated by smoke, without a need for exogenous inflammatory cells. Steroids, contrary to the usual belief, are able to ameliorate many of these changes, at least in this very acute model. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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