Fatty Acid Anabolism In Bronchial Epithelial Cells Modulates Airway Inflammation And Emphysema In COPD

Background: Chronic obstructive pulmonary disease(COPD)is characterized by incompletely reversible and progressive airflow obstruction,chronic airway inflammation,destruction of lung parenchyma,and is a common chronic airway disease accompanied with complications and systemic adverse reactions.The major risk factor for the occurrence and progression of COPD is cigarette smoking.Cigarette smoke(CS)exposure is known to induce the secretion of inflammatory factors and apoptosis in airway epithelial cells,leading to the persistent airway inflammation and progressive destruction of lung parenchyma.It is of great significance to study the role of airway epithelial cells in the occurrence and development of COPD.Clinical research found that COPD patients with low-weight is inclined to have emphysema compared with those over-weight subjects and higher body mass index(BMI)is a protective factor for the lung function of severe COPD patients.Above results suggest there are abnormal lipids metabolism in COPD patients and those changes may affect the prognosis of COPD.We all know that fatty acids are important raw for lipid synthesis.But whether there are changes in fatty acid metabolism in the whole body and the local airway of COPD patients and how do those changes influence the occurrence and progression of COPD? However,to date,there are scant relevant investigations.Objective: To investigate the influence of fatty acid anabolism in bronchial epithelial cells on the airway inflammation and emphysema of COPD.Methods: In vitro,western blot(WB)and quantitative real-time polymerase chain reaction(Q-PCR)were used to detect the changes of fatty acid synthesis associated signaling pathway-related molecules in the bronchial epithelial cells after CSE intervention,including sterol-regulatory element binding protein 1(SREBP1),fatty acid synthase(FASN),acetyl-Co A carboxylase1(ACC1),and stearyl-coenzyme A desaturase 1(SCD1).The levels of fatty acid and triglyceride in bronchial epithelial cells after CSE intervention were examined by relevant assay kit.Bronchial epithelial cells are pretreated with si RNA of fatty acid synthesis related molecules,the expression of inflammatory factors IL-6 and IL-8 induced by CSE in bronchial epithelial cells were tested by Q-PCR and Enzyme-linked immunosorbent assay(ELISA),meanwhile,the apoptosis of bronchial epithelial cells was detected by flow cytometry(FCM)and the levels of autophagy signaling pathway related molecules LC3B?and LC3B?were examined by WB.In vivo,a mouse model of COPD induced by cigarette smoke was constructed.Immunohistochemistry(IHC)and immunofluorescence(IF)were used to detect the expression of fatty acid synthesis associated molecules in bronchial epithelial cells of lung tissue in mice.Bronchial epithelial cells specific FASN deficient mice were used to identify the effect of fatty acid synthesis on the formation of chronic bronchial inflammation and destruction of lung parenchyma.Results: 1)Cigarette smoke exposure can cause the decrease of fatty acid and triglyceride in the serum of mice.2)Cigarette smoke exposure can cause the decrease of fatty acid and triglyceride in the lung tissue of mice.3)CSE can lead to the decrease of lipid in bronchial epithelial cells.4)CSE can reduce the synthesis of fatty acid in bronchial epithelial cells.5)The secretion of inflammatory factors of bronchial epithelial cells can be promoted by inhibiting the synthesis of fatty acid.6)The occurrence of apoptosis of bronchial epithelial cells can be promoted by inhibiting the synthesis of fatty acid.7)Autophagy can be promoted by inhibition of fatty acid synthesis in bronchial epithelial cells.Conclusion: Cigarette smoke exposure can lead to the decrease of fatty acid synthesis and lipid levels in bronchial epithelial cells,which result in the activation of autophagy,the secretion of inflammatory factors and the increase of apoptosis.The downregulation of fatty acid synthesis in bronchial epithelial cells promotes the occurrence and progression of COPD.