Zeldin Jordan, Tran Tan T, Yadav Manoj, Chaudhary Prem Prashant, D'Souza Brandon N, Ratley Grace, Ganesan Sundar, Myles Ian A
Epithelial Therapeutics Unit, National Institutes of Health, Bethesda, Maryland 20892, United States.
National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, United States.
Environ Sci Technol Lett. 2023 May 9;10(5):452-457. doi: 10.1021/acs.estlett.3c00142. Epub 2023 Apr 3.
Compared to the myriad of known triggers for rhinitis and asthma, environmental exposure research for atopic dermatitis (AD) is not well established. We recently reported that an untargeted search of U.S. Environmental Protection Agency (EPA) databases versus AD rates by United States (U.S.) postal codes revealed that isocyanates, such as toluene diisocyanate (TDI), are the pollutant class with the strongest spatiotemporal and epidemiologic association with AD. We further demonstrated that (di)isocyanates disrupt ceramide-family lipid production in commensal bacteria and activate the thermo-itch host receptor TRPA1. In this report, we reanalyzed regions of the U.S. with low levels of diisocyanate pollution to assess if a different chemical class may contribute. We identified antimony compounds as the top associated pollutant in such regions. Exposure to antimony compounds would be expected from brake dust in high-traffic areas, smelting plants, bottled water, and dust from aerosolized soil. Like TDI, antimony inhibited ceramide-family lipid production in and activated TRPA1 in human neurons. While further epidemiologic research will be needed to directly evaluate antimony exposure with surrounding AD prevalence and severity, these data suggest that compounds which are epidemiologically associated with AD, inhibit commensal lipid production, and activate TRPA1 may be causally related to AD pathogenesis.
与已知的引发鼻炎和哮喘的众多诱因相比，针对特应性皮炎（AD）的环境暴露研究尚不充分。我们最近报告称，通过对美国环境保护局（EPA）数据库与美国邮政编码对应的AD发病率进行非靶向搜索发现，异氰酸酯类，如甲苯二异氰酸酯（TDI），是与AD具有最强时空和流行病学关联的污染物类别。我们进一步证明，（二）异氰酸酯会破坏共生细菌中神经酰胺家族脂质的生成，并激活热痒宿主受体TRPA1。在本报告中，我们重新分析了美国异氰酸酯污染水平较低的地区，以评估是否有其他化学类别可能与之相关。我们确定锑化合物是这些地区最相关的污染物。在交通繁忙地区的制动粉尘、冶炼厂、瓶装水以及气雾化土壤产生的粉尘中都可能接触到锑化合物。与TDI一样，锑会抑制人神经元中神经酰胺家族脂质的生成并激活TRPA1。虽然需要进一步的流行病学研究来直接评估锑暴露与周围AD患病率和严重程度的关系，但这些数据表明，在流行病学上与AD相关、抑制共生脂质生成并激活TRPA1的化合物可能与AD发病机制存在因果关系。
