| First Author | Reynolds PR | Year | 2006 |
| Journal | Am J Respir Cell Mol Biol | Volume | 35 |
| Issue | 3 | Pages | 314-9 |
| PubMed ID | 16601242 | Mgi Jnum | J:125250 |
| Mgi Id | MGI:3757925 | Doi | 10.1165/rcmb.2005-0428OC |
| Citation | Reynolds PR, et al. (2006) Cigarette smoke-induced Egr-1 upregulates proinflammatory cytokines in pulmonary epithelial cells. Am J Respir Cell Mol Biol 35(3):314-9 |
| abstractText | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and is a progressive and irreversible disorder. Cigarette smoking is associated with 80-90% of COPD cases; however, the genes involved in COPD-associated emphysema and chronic inflammation are poorly understood. It was recently demonstrated that early growth response gene 1 (Egr-1) is significantly upregulated in the lungs of smokers with COPD (Ning W and coworkers, Proc Natl Acad Sci 2004;101:14895-14900). We hypothesized that Egr-1 is activated in pulmonary epithelial cells during exposure to cigarette smoke extract (CSE). Using immunohistochemistry, we demonstrated that pulmonary adenocarcinoma cells (A-549) and primary epithelial cells lacking basal Egr-1 markedly induce Egr-1 expression after CSE exposure. To evaluate Egr-1-specific effects, we used antisense (alphaS) oligodeoxynucleotides (ODN) to knock down Egr-1 expression. Incorporation of Egr-1 alphaS ODN significantly decreased CSE-induced Egr-1 mRNA and protein, while sense ODN had no effect. Via Egr-1-mediated mechanisms, IL-1beta and TNF-alpha were significantly upregulated in pulmonary epithelial cells exposed to CSE or transfected with Egr-1. To investigate the relationship between Egr-1 induction by smoking and susceptibility to emphysema, we determined Egr-1 expression in strains of mice with different susceptibilities for the development of smoking-induced emphysema. Egr-1 was markedly increased in the lungs of emphysema-susceptible AKR/J mice chronically exposed to cigarette smoke, but only minimally increased in resistant NZWLac/J mice. In conclusion, Egr-1 is induced by cigarette smoke and functions in proinflammatory mechanisms that likely contribute to the development of COPD in the lungs of smokers. |
