壬基苯酚對小鼠氣喘模式的影響-樹突狀細胞之研究

The effect of nonylphenol on murine asthma model – a dendritic cell study

林昌億(Chang-Yi Lin)

指導教授 ： 孫昭玲

高雄醫學大學/醫學院/醫學研究所/碩士(2011年)

https://doi.org/10.6832/KMU.2011.00139

摘要

前言：環境荷爾蒙廣泛存在於環境中，因其具有干擾荷爾蒙分泌系統之作用，環境荷爾蒙對生物的生殖和生理上都造成了一定程度的影響，其中壬基苯酚具有類雌激素活性，由於樹突細胞之分化與功能亦受雌激素影響，且樹突狀細胞在過敏性疾病扮演關鍵角色，因此推論壬基苯酚可藉由影響樹突狀細胞而加重過敏性氣喘之活性。
實驗方法：模擬人類暴露劑量與方式，每天餵食人類每日攝取容許( Tolerable Daily Intake；TDI )劑量5 ug/Kg給予正常BALB/c小鼠，經十天或二十天後分析脾臟免疫細胞族群之變化，與脾臟樹突狀細胞之功能變化，與氣喘動物模式之肺部發炎情形。
結果：在連續暴露壬基苯酚十天與二十天後，脾臟細胞中的族群分布除漿細胞樣樹突狀細胞外，其餘細胞沒有受到影響，漿細胞樣樹突狀細胞?vplasmacytoid DC?w的族群分布有增多現象。針對脾臟樹突狀細胞之功能性分析發現壬基苯酚的暴露會造成脾臟樹突狀細胞的成熟度下降，並且會分泌較高的發炎物質例如IL-6和TNF-?恁C此外也發現到暴露過壬基苯酚的脾臟樹突狀細胞會傾向驅使純真T細胞往TH2進行分化。在氣喘動物模式當中也可以看到連續暴露壬基苯酚的小鼠其肺沖洗液當中過敏相關的細胞如嗜酸性球以及淋巴球的數量高於控制組，而與氣喘相關的細胞激素如IL-4、IL-5和IL-13的分泌量有比較多。
結論：壬基苯酚的暴露會改變樹突狀細胞的功能，使其易誘導TH2細胞之分化，可能因此而增加氣喘的嚴重程度。我們的研究有助於釐清環境因子與人類過敏性疾病的因果關係。

關鍵字

壬基苯酚 ； 免疫

並列摘要

Abstract
Introduction
Endocrine disrupters are ubiquitously present in the human environment and have the property to disturb the endocrine system in different organisms. Nonylphenol (NP), one of endocrine disrupters, has been demonstrated that it has weak estrogenic activity. The function, differentiation and survival of dendritic cells (DCs) are also regulated by estrogen. Due to the important role of DCs in the pathogenesis of allergic asthma, we proposed that NP could alter the function of DCs and further enhance the disease activity of asthmatic lung inflammation.

Methods
To mimic the human exposure level and route and base on the human tolerable daily intake (TDI) of NP, BALB/c mice were orally delivered 5 ug NP /kg/day for 10 or 20 days. Splenic immune subsets were further analyzed in treated mice. Splenic DCs were purified to examine their functions. OVA-induced asthmatic lung inflammation was analyzed in treated mice.

Results
After 10-day or 20-day NP exposure, the percentages and numbers of splenic immune subsets were not significantly changed in the NP-exposed mice, except to plasmacytoid DCs (pDCs). The percentage of pDCs was increased in the NP-exposed mice. As to conventional DCs (cDCs), NP-exposure mediated the less immature phenotype and more IL-6 and TNF-a production of splenic cDCs. NP-exposed cDCs differentiated more naive T cells toward Th2 phenotype compared with corn oil-exposed cells. In addition, NP exposure enhanced the Th2-mediated eosinophil infiltration and Th2 cytokine pattern in brochoalveolar lavage fluid.

Conclusion
Our study suggests that endocrine disrupters, such as NP, have potential adverse effects on allergic diseases, at least in part by altering DC functions. This study will help us to provide a causal relationship between environmental exposure and the expression of allergic diseases.

並列關鍵字

nonylphenol ； immunity

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