PCBS & ESTROGENS ON PROINFLAMMATORY PHAGOCYTE FUNCTIONS

这是美国国立卫生研究院的一项区域提案，旨在检查环境影响 污染物对斑点叉尾鱼免疫功能的影响。与之相比 17β-雌二醇，一种强烈的雌激素，首席调查员将比较 代表3类污染物的化合物：壬基酚，一种外来雌激素； PCB126，与芳烃羟基酶受体结合的平面PCB126 (AHR)；以及PCB104，不与AHR结合的非平面PCB板。《校长》 研究人员假设外源雌激素和非平面多氯联苯抑制 吞噬细胞生理学，而平面多氯联苯通过AHR增强作用 促炎反应。进一步假设，非平面印刷电路板 会增强外源性雌激素对吞噬细胞功能的抑制作用 并拮抗平面多氯联苯产生的增强作用。吞噬细胞生理学 将在体外和体内暴露于这些化学物质后进行评估 细胞系和原代培养的叉尾鱼吞噬细胞。校长 要检查的终点包括吞噬作用、氧化爆发和Western 诱导型一氧化氮合酶、环氧合酶-2(COX-2)和 细胞色素P450同工酶CyP1a。此外，建议评估以下项目的效果： 环氧合酶-2和细胞色素P1a在苯并-α-芘代谢中的表达 两种酶将苯并-a-芘代谢成不同的产物。

This is an NIH AREA proposal to examine the effects environmental pollutants on immune function in the channel catfish. In comparison to 17beta-estradiol, a strong estrogen, the Principal Investigator will compare compounds representing 3 classes of pollutants: nonylphenol, a xenoestrogen; PCB 126, a planar PCB that binds to the aryl hydrocarbon hydroxylase receptor (Ahr); and PCB 104, a non-planar PCB that does not bind to Ahr. The Principal Investigator hypothesizes that xenoestrogens and non-planar PCBs suppress phagocyte physiology whereas planar PCBs acting through Ahr potentiate pro-inflammatory responses. It is further hypothesized that non-planar PCBs will potentiate the suppression of phagocyte function produced by xenoestrogens and antagonize the potentiation produced by planar PCBs. Phagocyte physiology will be assessed after both in vitro and in vivo exposure to these chemicals in cell lines and in primary cultures of catfish phagocytes. The principal endpoints to be examined include phagocytosis, oxidative burst, and Western blot analysis of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), and cytochrome P450 isozyme CYP1A. Further, it is proposed to assess the effect of changes of COX-2 and CYP1A expression on benzo-a-pyrene metabolism, since the two enzymes metabolize benzo-a-pyrene to different products.