| First Author | Roos AB | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 423 |
| Issue | 1 | Pages | 134-9 |
| PubMed ID | 22634316 | Mgi Jnum | J:185354 |
| Mgi Id | MGI:5428349 | Doi | 10.1016/j.bbrc.2012.05.096 |
| Citation | Roos AB, et al. (2012) Lung epithelial-C/EBPbeta contributes to LPS-induced inflammation and its suppression by formoterol. Biochem Biophys Res Commun 423(1):134-9 |
| abstractText | The inflammatory processes associated with pulmonary disorders remains incompletely understood. CCAAT/enhancer-binding protein (C/EBP)beta is implicated in inflammatory lung disorders as well as in beta(2)-adrenoceptor signaling. We hypothesized that C/EBPbeta in the lung epithelium contributes to lipopolysaccharide (LPS)-induced airway neutrophilia and expression of neutrophil chemoattractant chemokine (C-X-C) motif ligand (CXCL)1, as well as the suppressive effects of long-acting beta(2)-agonists (LABAs) and glucocorticoids (GCs). To investigate this, mice with a lung epithelial-specific deletion of C/EBPbeta (Cebpb(DeltaLE)) and control littermates (Cebpb(fl/fl)) were pre-treated with a LABA, formoterol and/or a GC, budesonide, and challenged with LPS. Inflammatory cell recruitment in bronchoalveolar lavage (BAL) fluid and pulmonary expression of inflammatory mediators were investigated. In addition, the ability of formoterol to increase C/EBP transactivation was assessed in vitro. LPS-challenged Cebpb(DeltaLE) mice exhibited fewer BAL neutrophils and lower pulmonary expression of CXCL1 versus Cebpb(fl/fl) mice. Suppression of LPS-induced neutrophilia by formoterol was impaired in Cebpb(DeltaLE) mice and Cxcl1 expression was increased. However, suppression of the neutrophilia by budesonide with/without formoterol was preserved. Further studies indicated that C/EBP transactivation was increased by the cAMP elevating agent forskolin and formoterol in a beta(2)-adrenoceptor dependent manner. Thus, C/EBPbeta in the lung epithelium contributes to LPS-induced CXCL1 expression and airway neutrophilia as well as to the suppressive effects of formoterol. Reduced C/EBPbeta activity, observed in smokers with chronic obstructive pulmonary disease, may impair the responsiveness to LABAs when used without GCs. |
