Association between Genetic Variants of Transforming Growth Factor-β1 and Susceptibility of Pneumoconiosis: A Meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transforming growth factor-beta 1 (TGF-β1) and gene variants have been extensively studied in various human diseases. For example, TGF-β1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-β1 -509 C>T [rs1800469], +869 T>C [rs1800470], and +915 G>C [rs1800471] polymorphisms and pneumoconiosis.</p><p><b>METHODS</b>A comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu (Chinese) Database by the end of April 2016. Eleven publications with 21 studies were included in this meta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 (StataCorp, College Station, TX, USA) software.</p><p><b>RESULTS</b>The data showed significant associations between TGF-β1 -509 C>T polymorphism and the risk of pneumoconiosis development (T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.00-1.81, P = 0.046); between TGF-β1 +915 G>C polymorphism and the pneumoconiosis risk (C vs. G, OR = 1.69, 95% CI: 1.19-2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI: 1.23-2.60, P = 0.002; CC+CG vs. GG, OR = 1.80, 95% CI: 1.24-2.61, P = 0.002). In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers' pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-β1 +869 T>C polymorphism and risk of pneumoconiosis.</p><p><b>CONCLUSION</b>The polymorphisms of both TGF-β1 -509 C>T and +915 G>C are associated with increased risk of pneumoconiosis.</p>

Inhibiting autophagy of dendritic cells meliorates asthma in mice / 第二军医大学学报

Objective To study the impact of autophagy inhibition on functions of dendritic cells (DCs) and mouse model of allergic asthma. Methods (1)BALB/c mice were divided into three groups using the random number table: asthma model group, asthma treated with autophagy inhibitor (chloroquine) group (asthma+CQ group) and control group. Mouse models in asthma group and asthma+CQ group were induced with ovalbumin (OVA); meanwhile, mice of asthma+CQ group were also treated with autophagy inhibitor CQ. Hematoxylin-Eosin (H-E) staining was used to observe the pathological changes in lung tissues of mice. ELISA, Western blotting analysis and flow cytometery were used to detect the serum OVA-specific IgE, autophagy level, and expression of surface co-stimulatory molecules and major histocompatibility complex class H (MHC H ) on lung DCs, respectively. (2)Bone marrow-derived DCs were treated with autophagy inhibitor 3-methyladenine (3MA) in vitro and the surface expression of co-stimulatory molecules and MHC H was detected. (3) We sorted CD4+ T cells from spleens of OT2 mice, then co-cultured with lung DCs from mice of different groups (T cells: DCs=1: 10), and detected the activation and proliferation of T cells with flow cytometery. Results (1) The level of OVA-specific IgE (P < 0. 05), extent of inflammatory cell infiltration in lung tissues, autophagy level in lung DCs (P<0. 05), and expression of CD86 and MHCH (P<0. 05)on lung DCs in asthma + CQ group were significantly lower than those in the asthma group. (2) 3MA treatment decreased the surface expression of CD86 and MHC" on bone marrow-derived DCs (P<0. 05). And (3) lung DCs from asthma+CQ group had lower ability for activating T cells and promoting T cell proliferation than those from the asthma group (P<0. 05). Conclusion Autophagy inhibitors can improve the pathologic condition of allergic asthma through inhibiting autophagy in DCs, down-regulating surface expression of co stimulatory molecules and MHC" on DCs, and further inhibiting the DCs-induced proliferation of T cells.