SFTPB regulates PTGS2 and inflammation in chronic obstructive pulmonary disease

New findings What is the central question of this study? It is reported that SFTPB polymorphisms are associated with COPD. The function and its mechanism of SFTPB in COPD are still unknown. We indicate the function and underlying mechanism in controls and COPD patients, A549 cells induced by 10% CSE and a mouse model of COPD. Furthermore, we have indicated the mechanism of SFTPB in COPD by regulating the expression of SFTPB in A549 cells. What is the main finding and its importance? Under the stimulation of the risk factors of COPD, SFTPB expression is decreased, which may be involved in the formation of COPD. The progress of COPD induces an inflammatory response and reduces SFTPB expression. Otherwise, levels of PTGS2 and inflammatory responses are changed by SFTPB, which indicates that SFTPB promotes the progression of COPD by PTGS2 and inflammation. Abstract Pulmonary surfactant-associated protein B (SFTPB) is a critical protein for lung homeostasis, and its polymorphisms are associated with COPD. However, few studies have so far confirmed the functional involvement of SFTPB in COPD. Serum SFTPB and inflammatory cytokines levels were measured in 54 patients with acute exacerbation of COPD and 29 healthy controls. A549 cells were induced using 10% cigarette smoke extract (CSE) and treated with dexamethasone to investigate the effect of inflammation on SFTPB expression, and the effect of SFTPB overexpression and silencing on inflammatory cytokines was measured using real-time PCR and ELISA. Lastly, SFTPB expression was assessed in mouse lung tissues using immunofluorescence. Serum levels of SFTPB were significantly lower in COPD patients than in controls (p = 0.009). Conversely, levels of IL-6 and prostaglandin-endoperoxide synthase-2 (PTGS2) were increased in COPD patients (IL-6: p = 0.006, PTGS2: p = 0.043). After CSE treatment, SFTPB mRNA and protein levels were significantly decreased compared to controls (mRNA: p = 0.002; protein: p = 0.011), while IL-6, IL-8 and PTGS2 were elevated. Dexamethasone treatment increased SFTPB levels. Following SFTPB overexpression in A549 cells, mRNA and protein levels of IL-6, IL-8 and PTGS2 were significantly reduced, while silencing induced the opposite effect. SFTPB levels were significantly reduced in the lung tissue of a mouse model of COPD compared to controls. Reduced SFTPB levels may induce PTGS2 and inflammatory responses in COPD and could be a key protein for evaluation of COPD progression. This article is protected by copyright. All rights reserved.