PCBS & ESTROGENS ON PROINFLAMMATORY PHAGOCYTE FUNCTIONS

这是一项研究环境影响的NIH区域提案

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.