Modification of the rat airway explant transcriptome by cigarette smoke.
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.
López-Boado
Yolanda S
YS
GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
Li
Jun U
JU
Clayton
Chris L
CL
Wright
Joanne L
JL
Churg
Andrew
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004848:Epithelium / Q000473:pathology; D005784:Gene Amplification; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
D000893:Anti-Inflammatory Agents; D016877:Oxidants; D012906:Smoke; D012313:RNA; D003907:Dexamethasone