Inamdar Arati A, Bennett Joan W
Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, 08901.
Sci Rep. 2014 Feb 10;4:3833. doi: 10.1038/srep03833.
Using a Drosophila model, we previously demonstrated truncated life span and neurotoxicity with exposure to 1-octen-3-ol, the volatile organic compound (VOC) responsible for much of the musty odor found in mold-contaminated indoor spaces. In this report, using biochemical and immunological assays, we show that exposure to 0.5 ppm 1-octen-3-ol induces a nitric oxide (NO) mediated inflammatory response in hemocytes, Drosophila innate immune cells. Moreover, exposed Drosophila brains show increased peroxynitrite expression. An increase in nitrite levels is observed with toluene and 1-octen-3-ol but not with 1-butanol. Pharmacological inhibitors of nitric oxide synthase (NOS) namely, L-NAME, D-NAME and minocycline, and NOS mutants show improvements of life span among 1-octen-3-ol exposed flies. Exposure to 1-octen-3-ol also induces NOS expression in larval tracheal tissues and remodels tracheal epithelial lining. These findings suggest a possible mechanistic basis for some of the reported adverse health effects attributed to mold exposure and demonstrates the utility of this in vivo Drosophila model to complement existing model systems for understanding the role of inflammation in VOC-mediated toxicity.
我们之前利用果蝇模型证明，暴露于1-辛烯-3-醇（这种挥发性有机化合物（VOC）是霉菌污染室内空间中大部分霉味的来源）会导致寿命缩短和神经毒性。在本报告中，我们通过生化和免疫分析表明，暴露于0.5 ppm的1-辛烯-3-醇会在血细胞（果蝇的固有免疫细胞）中诱导一氧化氮（NO）介导的炎症反应。此外，暴露后的果蝇大脑中过氧亚硝酸盐表达增加。甲苯和1-辛烯-3-醇会使亚硝酸盐水平升高，但1-丁醇不会。一氧化氮合酶（NOS）的药理学抑制剂，即L-NAME、D-NAME和米诺环素，以及NOS突变体，在暴露于1-辛烯-3-醇的果蝇中显示出寿命延长。暴露于1-辛烯-3-醇还会诱导幼虫气管组织中的NOS表达，并重塑气管上皮内衬。这些发现为一些报道的与接触霉菌有关的不良健康影响提供了可能的机制基础，并证明了这种体内果蝇模型在补充现有模型系统以理解炎症在VOC介导的毒性中的作用方面的实用性。
