Li Ruijin, Meng Ziqiang
Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China.
Arch Toxicol. 2007 Dec;81(12):867-74. doi: 10.1007/s00204-007-0212-7. Epub 2007 May 23.
Sulfur dioxide (SO2) is a common air pollutant, and inhaled SO2 in airway epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite), which are toxic to the respiratory system and related to the exacerbation of asthma. To investigate the effects of SO2 derivatives on the expressions of asthma related genes (MUC5AC and IL-13), the mRNA and protein levels of the two genes in cultured human bronchial epithelial (BEP2D) cells were analyzed using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay, immunocytochemistry method and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the mRNA expressions of MUC5AC and IL-13 were significantly increased at different concentrations of SO2 derivatives (0.0001, 0.001, 0.01, 0.1 and 1.0 mM), and the maximum appeared at 0.01 mM for MUC5AC (3.9-fold) or at 0.001 mM for IL-13 (4.7-fold). Meanwhile, SO2 derivatives significantly increased the mRNA levels at 0, 0.5, 1, 4 and 24 h post-exposure with the maximum at 4 h post-exposure (25-fold for MUC5AC and 41-fold for IL-13). Furthermore, the protein levels of MUC5AC and IL-13 in BEP2D cells were significantly increased at different concentrations and different time courses exposed to SO2 derivatives, along with the maximum at 4 h post-exposure. These results lead to a conclusion that SO2 derivatives can increase the expressions of MUC5AC and IL-13 genes on the transcription and translation levels, and it suggests that SO2 derivatives can induce mucus over-production and inflammation responses in human bronchial epithelial cells and may have relations with asthma diseases. This might be one of the possible mechanisms that SO2 aggravates asthma disease.
二氧化硫（SO₂）是一种常见的空气污染物，呼吸道上皮吸入的SO₂在体内易形成其可溶性衍生物（亚硫酸氢盐和亚硫酸盐），这些衍生物对呼吸系统有毒性且与哮喘加重有关。为研究SO₂衍生物对哮喘相关基因（MUC5AC和IL - 13）表达的影响，分别采用实时逆转录 - 聚合酶链反应（实时RT - PCR）检测、免疫细胞化学方法和酶联免疫吸附测定（ELISA）分析了培养的人支气管上皮（BEP2D）细胞中这两个基因的mRNA和蛋白质水平。结果显示，在不同浓度的SO₂衍生物（0.0001、0.001、0.01、0.1和1.0 mM）作用下，MUC5AC和IL - 13的mRNA表达显著增加，MUC5AC在0.01 mM时达到最大值（3.9倍），IL - 13在0.001 mM时达到最大值（4.7倍）。同时，暴露后0、0.5、1、4和24小时，SO₂衍生物显著增加了mRNA水平，在暴露后4小时达到最大值（MUC5AC为25倍，IL - 13为41倍）。此外，在不同浓度和不同时间进程暴露于SO₂衍生物时，BEP2D细胞中MUC5AC和IL - 13的蛋白质水平显著增加，在暴露后4小时达到最大值。这些结果得出结论，SO₂衍生物可在转录和翻译水平上增加MUC5AC和IL - 13基因的表达，这表明SO₂衍生物可诱导人支气管上皮细胞中黏液过度产生和炎症反应，可能与哮喘疾病有关。这可能是SO₂加重哮喘疾病的一种可能机制。
