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Expression of HMGB1 in maternal exposure to fine particulate air pollution induces lung injury in rat offspring assessed with micro-CT.
Chemico-biological Interactions 2018 January 26
OBJECTIVES: Maternal particulate matter with less than 2.5 μm in diameter (PM2.5) is associated with an increased risk for acute lower respiratory infections and allergic airway inflammation; however, its effect on the developing lung remains unclear. The aim of this study is to determine the effect of maternal PM2.5 during pregnancy on lung development in offspring.
METHODS: Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5 mg/kg) once every 3 days from day 0-18 of pregnancy and delivered at term. Lungs were obtained on postnatal day 0, the structure of the lung was analyzed by quantitative micro-computed tomography (CT) and the levels of proinflammatory cytokines were analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of high mobility group box-1 (HMGB1) was also detected by immunohistochemistry, Western blotting, and quantitative RT-PCR.
RESULTS: Ground-glass opacity and high-density volumes in CT slice images of maternal PM2.5-exposure rats were observed. The concentrations of IL-1, IL-6 and TNF-α were significantly increased by 2.36-, 3.91- and 4.36-fold, respectively, in the rats of the PM-7.5 group compared with the rats in the control group. The PM2.5-treated rats showed a significant upregulated expression of HMGB1 in lungs.
CONCLUSIONS: PM2.5 exposure during pregnancy results in lung inflammation in offspring mediated by increased HMGB1 expression, followed by upregulated IL-1, IL-6 and TNF-α secretions, which may contribute to the development of inflammatory lung diseases in later life.
METHODS: Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5 mg/kg) once every 3 days from day 0-18 of pregnancy and delivered at term. Lungs were obtained on postnatal day 0, the structure of the lung was analyzed by quantitative micro-computed tomography (CT) and the levels of proinflammatory cytokines were analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of high mobility group box-1 (HMGB1) was also detected by immunohistochemistry, Western blotting, and quantitative RT-PCR.
RESULTS: Ground-glass opacity and high-density volumes in CT slice images of maternal PM2.5-exposure rats were observed. The concentrations of IL-1, IL-6 and TNF-α were significantly increased by 2.36-, 3.91- and 4.36-fold, respectively, in the rats of the PM-7.5 group compared with the rats in the control group. The PM2.5-treated rats showed a significant upregulated expression of HMGB1 in lungs.
CONCLUSIONS: PM2.5 exposure during pregnancy results in lung inflammation in offspring mediated by increased HMGB1 expression, followed by upregulated IL-1, IL-6 and TNF-α secretions, which may contribute to the development of inflammatory lung diseases in later life.
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