| First Author | Didon L | Year | 2011 |
| Journal | Am J Respir Crit Care Med | Volume | 184 |
| Issue | 2 | Pages | 233-42 |
| PubMed ID | 21562127 | Mgi Jnum | J:267247 |
| Mgi Id | MGI:6260100 | Doi | 10.1164/rccm.201007-1113OC |
| Citation | Didon L, et al. (2011) Lung epithelial CCAAT/enhancer-binding protein-beta is necessary for the integrity of inflammatory responses to cigarette smoke. Am J Respir Crit Care Med 184(2):233-42 |
| abstractText | RATIONALE: Cigarette smoke is the major cause of chronic obstructive pulmonary disease and lung cancer. The mechanisms by which smoking induces pulmonary dysfunction are complex, involving stress from toxic components and inflammatory responses. Although CCCAAT/enhancer-binding protein (C/EBP)-beta is known as a key intracellular regulator of inflammatory signaling, its role in pulmonary inflammation has not been established. OBJECTIVES: To characterize the role of C/EBPbeta in the airway epithelial response to cigarette smoke. METHODS: mRNA expression in the airway epithelium of current, former, and never-smokers, and in in vitro cigarette smoke extract-treated primary human airway epithelial cells, was analyzed by microarray and quantitative real-time polymerase chain reaction, respectively. Mice with lung epithelial-specific inactivation of C/EBPbeta were generated and exposed to cigarette smoke for 4 or 11 days. Lung histology, bronchoalveolar lavage cell differentials, and expression of inflammatory and innate immune mediators in the lungs were assessed. MEASUREMENTS AND MAIN RESULTS: C/EBPbeta was significantly down-regulated in the airway epithelium of both current and former smokers compared with never-smokers, and in cigarette smoke-treated primary human airway epithelial cells in vitro. Cigarette smoke-exposed mice with a lung epithelial-specific inactivation of C/EBPbeta displayed blunted respiratory neutrophil influx and compromised induction of neutrophil chemoattractants growth-regulated oncogene-alpha, macrophage inflammatory protein-1gamma, granulocyte colony-stimulating factor, and serum amyloid A 3 and proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, compared with smoke-exposed controls. Inhibition of C/EBPbeta in human airway cells in vitro caused a similarly compromised response to smoke. CONCLUSION: Our data suggest a previously unknown role for C/EBPbeta and the airway epithelium in mediating inflammatory and innate immune responses to cigarette smoke. |
