کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1929451 | 1050459 | 2012 | 6 صفحه PDF | دانلود رایگان |
The inflammatory processes associated with pulmonary disorders remains incompletely understood. CCAAT/enhancer-binding protein (C/EBP)β is implicated in inflammatory lung disorders as well as in β2-adrenoceptor signaling. We hypothesized that C/EBPβ 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 β2-agonists (LABAs) and glucocorticoids (GCs).To investigate this, mice with a lung epithelial-specific deletion of C/EBPβ (CebpbΔLE) and control littermates (Cebpbfl/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 CebpbΔLE mice exhibited fewer BAL neutrophils and lower pulmonary expression of CXCL1 versus Cebpbfl/fl mice. Suppression of LPS-induced neutrophilia by formoterol was impaired in CebpbΔLE 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 β2-adrenoceptor dependent manner.Thus, C/EBPβ in the lung epithelium contributes to LPS-induced CXCL1 expression and airway neutrophilia as well as to the suppressive effects of formoterol. Reduced C/EBPβ activity, observed in smokers with chronic obstructive pulmonary disease, may impair the responsiveness to LABAs when used without GCs.
► We examined C/EBPβ in pulmonary inflammation and suppression by formoterol.
► C/EBPβ contributes to LPS-induced pulmonary neutrophilia and CXCL1 expression.
► C/EBPβ plays a role in suppression of Cxcl1 and Il6 by formoterol.
► We propose that C/EBPβ contributes to both pro- and anti-inflammatory effects.
Journal: Biochemical and Biophysical Research Communications - Volume 423, Issue 1, 22 June 2012, Pages 134–139