Modification of the rat airway explant transcriptome by cigarette smoke.

Abstract

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.

• Authors: Yolanda S López-Boado, Jun U Li, Chris L Clayton, Joanne L Wright, Andrew Churg
• Journal: Inhalation toxicology (Inhal Toxicol) Vol. 22 Issue 3 Pg. 234-44 (Feb 2010) ISSN: 1091-7691 [Electronic] England
• PMID: 19883206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Oxidants
• Smoke
• RNA
• Dexamethasone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Dexamethasone (pharmacology)
• Epithelium (pathology)
• Gene Amplification
• Gene Expression (drug effects)
• Gene Expression Profiling
• Oligonucleotide Array Sequence Analysis
• Organ Culture Techniques
• Oxidants (toxicity)
• Oxidative Stress (drug effects)
• RNA (biosynthesis, isolation & purification)
• Rats
• Rats, Sprague-Dawley
• Respiratory System (metabolism, pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Smoke (adverse effects)
• Smoking (adverse effects)
• Tobacco (adverse effects)