Details

Autor(en) / Beteiligte

• Wu, Gaohui
• Yang, Liteng
• Xu, Yi
• Jiang, Xiaohong
• Jiang, Xiaomin
• Huang, Lisha
• Mao, Ling
• Cai, Shaoxi

Titel

FABP4 induces asthmatic airway epithelial barrier dysfunction via ROS-activated FoxM1

Ist Teil von

• Biochemical and biophysical research communications, 2018-01, Vol.495 (1), p.1432-1439

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Functional abnormal airway epithelial cells, along with activated inflammatory cells, resulting in chronic airway inflammation, are considered as the characteristic of asthma. Fatty Acid Binding Protein 4 (FABP4) takes part in glucose and lipid homeostasis, and also have an important role in allergic airway inflammation. However, whether FABP4 influence barrier function of airway epithelial cells is unknown. In vivo, a HDM-induced murine model of asthma was obtained to assessed airway inflammation and protein expression of E-cadherin and Forkhead Box M1 (FoxM1). In vitro, 16-HBE was cultured and was treated with hrFABP4, siFABP4, FABPF4 inhibitor BMS, or FoxM1 inhibitor RCM-1. IL-4, IL-5, and IL-13 level was determined by ELISA. Transepithelial electrical resistance (TER), paracellular permeability and E-cadherin-special immunofluorescence were measured to value airway epithelial barrier function. Intracellular ROS production was determined by DCF-DA fluorescence. FABP4 inhibitor BMS alleviate airway inflammation and destruction of E-cad in allergic mouse. Treatment with HDM or hrFABP4 aggravated inflammatory response, damaged airway epithelial barrier, which could be inhibited by siFABP4 and BMS. Treatment with HDM or hrFABP4 also enhanced levels of FoxM1, and Inhibited FoxM1 suppressed HDM- and hrFABP4-induced inflammation and airway epithelial barrier dysfunction. In addition, H2O2 promoted FoxM1 expression, HDM and hrFABP4 induced-FoxM1 could be inhibited by NAC, leading to decreased inflammation and improved airway epithelial barrier. Upregulated ROS induced by FABP4 was of significance in activating FoxM1 leading to airway inflammation and epithelial barrier dysfunction. •FABP4 plays an important role in airway inflammatory cytokine production and airway barrier integrity.•FoxM1 is an important participant in FABP4-induced airway inflammation and epithelial barrier dysfunction.•Upregulated ROS induced by FABP4 is of significance in activating FoxM1.