Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children.
Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children.
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DOI：
10.1186/1868-7083-4-17
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发表时间：
2012-09-25
影响因子：
5.7
通讯作者：
Nadeau K
中科院分区：
文献类型：
--
作者：
Kohli A;Garcia MA;Miller RL;Maher C;Humblet O;Hammond SK;Nadeau K
二手烟 (SHS) 和环境空气污染 (AAP) 暴露与哮喘患病率和严重程度增加以及免疫细胞 DNA 改变有关。在当前的研究中，我们检查了 SHS 和 AAP 与 T 细胞群中 DNA 甲基化以及干扰素-γ (IFN-γ) 和叉头盒蛋白 3 (Foxp3) 表达的关系。 7-18岁的受试者从弗雷斯诺（高 AAP；n = 62）和加利福尼亚州斯坦福（低 AAP；n = 40）招募，并分为 SHS 暴露组（弗雷斯诺：n = 31，斯坦福大学：n = 6）和非 SHS 暴露组（nSHS；弗雷斯诺： n = 31，斯坦福大学：n = 34）组。评估从外周血纯化的 T 细胞的 DNA 甲基化水平和 IFN-γ（效应 T 细胞）或 Foxp3（调节 T 细胞）的表达水平。分析显示，与 SHS 暴露相关的 IFN-γ 和 Foxp3 的平均 CpG 甲基化百分比显着增加（IFN-γ：FSHS 62.10%，FnSHS 41.29%，p < 0.05；SSHS 46.67%，SnSHS 24.85%，p < 0.05；Foxp3：FSHS 74.60%，FnSHS 54.44%，p < 0.05；SSHS 62.40%，SnSHS 18.41%，p < 0.05），并且两个基因的平均转录水平显着降低（IFN-γ：FSHS 0.75，FnSHS 1.52，p< 0.05；SHS） 2.25，nSHS 3.53，p < 0.05；Foxp3：FSHS 0.75，FnSHS 3.29，p < 0.05；SSHS 4.8，SnSHS 7.2，p< 0.05）。 AAP 还与高甲基化相关（IFN-γ：FSHS 与 SSHS，p < 0.05；FnSHS 与 SnSHS，p < 0.05；Foxp3：FSHS 与 SSHS，p < 0.05；FnSHS 与 SnSHS，p < 0.05）以及两个基因的转录减少（IFN-γ：FSHS 与 SSHS，p < 0.05；FnSHS 与 SnSHS，p < 0.05；Foxp3：FSHS 与 SSHS，p < 0.05；FnSHS 与 SnSHS，p < 0.05）。仅 AAP 和仅 SHS 暴露之间的平均甲基化没有显着差异（IFN-γ：p = 0.15；Foxp3：p = 0.27），Foxp3 表达也没有显着差异（p = 0.08）；仅使用 AAP 的受试者中 IFN-γ 表达显着降低 (p<<0.05)。暴露于 SHS 和 AAP 与 Teffs 中的 IFN-γ 和 Tregs 中的 Foxp3 的显着高甲基化和表达降低有关。每次暴露对 DNA 修饰和哮喘发病机制的相对贡献值得进一步研究。
Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined the association between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN-γ) and forkhead box protein 3 (Foxp3) in T cell populations. Subjects 7–18 years old were recruited from Fresno (high AAP; n = 62) and Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31, Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34) groups. T cells purified from peripheral blood were assessed for levels of DNA methylation and expression of IFN-γ (in effector T cells) or Foxp3 (in regulatory T cells). Analysis showed a significant increase in mean % CpG methylation of IFN-γ and Foxp3 associated with SHS exposure (IFN-γ: FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3: FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a significant decrease in mean transcription levels of both genes (IFN-γ: FSHS 0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75, FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated with hypermethylation (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased transcription of both genes (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average methylation between AAP- and SHS-only exposures was not significantly different (IFN-γ: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN-γ expression was significantly decreased in AAP-only subjects (p < 0.05). Exposures to SHS and AAP are associated with significant hypermethylation and decreased expression of IFN-γ in Teffs and Foxp3 in Tregs. Relative contributions of each exposure to DNA modification and asthma pathogenesis warrant further investigation.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
影响因子：
3.7
作者：
Guerrero-Preston, Rafael;Goldman, Lynn R.;Sidransky, David
通讯作者：
Sidransky, David
影响因子：
3.7
作者：
Janson PC;Winerdal ME;Marits P;Thörn M;Ohlsson R;Winqvist O
通讯作者：
Winqvist O
影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf