NF-κB Interacts With KGF And TGF-β1 In Regulating Airway Remodeling Of Mice Exposed To Acrolein

Objective:To investigate the effect of quercetin and caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB on airway remodeling of mice inhaled with acrolein fog for six weeks.To explore the role of keratinocyte growth factor(KGF) and the interaction of KGF and TGF-β1 through NF-κB pathway in airway remodeling.Methods: Airway remodeling model of mice was established with acrolein inhalation 6 h per day for six weeks. Ninety-six C57BL/6 mice were randomly divided into eight groups and six mice in each groupe.Mice with or without acrolein inlation were intraperitonealy injected with CAPE 30 mg/kg qod or quercetin 0.2g/kg qod. Mice were also administered with saline for normal control or DMSO as solvent control. Lung tissue sections were stained with HE, Masson and evaluated with Ashcroft scores. Hydroxyproline concentration of lung tissues was assayed. Total and differential cell count,the level of IL-1a,TGF-61,and IFN-γconcentration in BALF were examined by microscopy and ELISA, respectively. Nuclear factor-κB, I-κB, KGF, Smad7, and TGF-81 in bronchial epithelia were detected by immunohistochemistry, Western blot or RT-PCR.Results: Comparing with control, increased airway inflammation, smooth muscle cell proliferation and sub-epithelial collagen deposition were observed in mice inhaled with acrolein fog (P<0.05), which was significantly reduced after the treatment with quercetin and CAPE (P<0.05) .Acrolein increased staining of NF-κB in cytoplasm and the ratio of nuclear transposition in bronchial epithelial cells was decreased after the administration of quercetin and CAPE (P<0.05) .Quercetin and CAPE increase the expression of I-κB and Smad7 in cytoplasm. Accordingly, the increased expression of KGF mRNA and protein in mice treated with quercetin and CAPE.The upregulated expression of NF-κB protein in bronchial epithelial cells was positively correlated with the level of cytokine IL-1a and TGF-β1, but negatively correlated with the IFN-γ.The upregulated expression of KGF mRNA in bronchial epithelial cells was negatively correlated with the TGF-β1.Conclusion: Mice exposed to acrolein for six weeks results in chronic airway inflammatory injury and airway remodeling.Both quercetin and NF-κB inhibitor CAPE inhibit acrolein-induced airway inflammation and the development of airway remodeling,which was complicated the upregulation of KGF expression,and down-regulate of TGF-β1 expression.The modulation of airway remodeling by NF-κB may be through the inrease release of active IL-la and TGF-β1,and decrease the release of IFN-γ.The interaction of NF-kB,KGF and TGF-β1 pathway regulate airway inflammation and remodeling in mice exposed to acrolein.