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简介：AbstractBackground:Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods:Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes.Results:Testosterone was negatively related to periostin (ρ = -0.420, P = 0.009) and IL-5 (ρ = -0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage (ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males (ρ = 0.943, P = 0.005) but negative in females (ρ = -0.561, P = 0.030).Conclusions:Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

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简介：AbstractBackground:Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods:In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1 (P < 0.001) and plasmid-MCPIP1 (P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.