Ozone exposure alters serotonin and serotonin receptor expression in the developing lung.
Ozone exposure alters serotonin and serotonin receptor expression in the developing lung.
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臭氧暴露会改变发育中肺部的血清素和血清素受体表达。
DOI：
10.1093/toxsci/kft090
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
VanWinkle,LauraS
中科院分区：
文献类型：
--
作者：
Murphy,ShannonR;Schelegle,EdwardS;Miller,LisaA;Hyde,DallasM;VanWinkle,LauraS
臭氧是一种普遍存在的环境污染物，对儿童的肺功能发育有不利影响。动物研究表明，改变的肺发育与气道上皮间充质营养单位内的修饰信号有关，包括可以改变神经生长的介质。我们假设臭氧暴露改变了血清素、其转运体（5-HTT）和两个关键受体（5-HT 2A和5-HT 4）的正常模式，这是一种参与出生后气道神经、上皮和免疫过程的途径。我们将猴子在生命的前2个月或6个月暴露于急性或间歇性臭氧中。有三个暴露组/年龄：（1）过滤空气，（2）急性臭氧挑战，（3）间歇性臭氧+急性臭氧挑战。制备肺用于区室特异性qRT-PCR、免疫组织化学和体视学。所有暴露组的气道上皮5-羟色胺免疫阳性染色均增加，其中2个月中段和6个月远端气道最为突出。5-HTT、5-HT 2AR和5-HT 4 R的基因表达以年龄依赖性方式增加。与中段气道相比，远端气道的总体表达更高。臭氧暴露破坏了气道中5-HT 2AR和5-HT 4 R蛋白的表达，并增强了平滑肌上5-HT 2AR（2个月）和5-HT 4 R（6个月）的免疫阳性染色。臭氧暴露会增加气道上皮中的5-羟色胺，而与气道水平、年龄和暴露史无关，并会改变5-羟色胺受体蛋白（5-HT 2A和5-HT 4）和5-HTT基因表达的空间模式，这取决于隔室、年龄和暴露史。了解血清素如何调节臭氧暴露加剧的可逆性气道阻塞的成分，为开发气道疾病的临床相关疗法奠定了基础。
Ozone, a pervasive environmental pollutant, adversely affects functional lung growth in children. Animal studies demonstrate that altered lung development is associated with modified signaling within the airway epithelial mesenchymal trophic unit, including mediators that can change nerve growth. We hypothesized that ozone exposure alters the normal pattern of serotonin, its transporter (5-HTT), and two key receptors (5-HT2Aand 5-HT4), a pathway involved in postnatal airway neural, epithelial, and immune processes. We exposed monkeys to acute or episodic ozone during the first 2 or 6 months of life. There were three exposure groups/age: (1) filtered air, (2) acute ozone challenge, and (3) episodic ozone + acute ozone challenge. Lungs were prepared for compartment-specific qRT-PCR, immunohistochemistry, and stereology. Airway epithelial serotonin immunopositive staining increased in all exposure groups with the most prominent in 2-month midlevel and 6-month distal airways. Gene expression of 5-HTT, 5-HT2AR, and 5-HT4R increased in an age-dependent manner. Overall expression was greater in distal compared with midlevel airways. Ozone exposure disrupted both 5-HT2AR and 5-HT4R protein expression in airways and enhanced immunopositive staining for 5-HT2AR (2 months) and 5-HT4R (6 months) on smooth muscle. Ozone exposure increases serotonin in airway epithelium regardless of airway level, age, and exposure history and changes the spatial pattern of serotonin receptor protein (5-HT2Aand 5-HT4) and 5-HTT gene expression depending on compartment, age, and exposure history. Understanding how serotonin modulates components of reversible airway obstruction exacerbated by ozone exposure sets the foundation for developing clinically relevant therapies for airway disease.
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DOI：
10.1164/ajrccm.161.6.9908102
发表时间：
2000-06
影响因子：
24.7
作者：
R. Jörres;O. Holz;W. Zachgo;P. Timm;S. Koschyk;Bernd Müller;F. Grimminger;W. Seeger;F. Kelly;C. Dunster;T. Frischer;Gerd Lubec;Marc Waschewski;A. Niendorf;H. Magnussen
通讯作者：
R. Jörres;O. Holz;W. Zachgo;P. Timm;S. Koschyk;Bernd Müller;F. Grimminger;W. Seeger;F. Kelly;C. Dunster;T. Frischer;Gerd Lubec;Marc Waschewski;A. Niendorf;H. Magnussen
影响因子：
6.7
作者：
Lechin, F;van der Dijs, B;Lechin, AE
通讯作者：
Lechin, AE
肺部血清素的存在及其在过敏反应中的意义。
影响因子：
56.9
作者：
H. Weissbach;T. Waalkes;S. Udenfriend
通讯作者：
S. Udenfriend
培养的豚鼠气道平滑肌细胞对血清素的吸收和代谢。
影响因子：
3.2
作者：
A. Dodson;G. Anderson;K. Rhoden
通讯作者：
K. Rhoden
影响因子：
0.6
作者：
J. Brain
通讯作者：
J. Brain