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多氯联苯126影响虹鳟鱼前肾细胞原代培养物中参与应激-免疫相互作用的基因表达。

Polychlorinated biphenyl 126 affects expression of genes involved in stress-immune interaction in primary cultures of rainbow trout anterior kidney cells.

作者信息

Quabius Elgar Susanne, Krupp Guido, Secombes Christopher J

机构信息

Scottish Fish Immunology Research Centre, University of Aberdeen, Scotland, United Kingdom.

出版信息

Environ Toxicol Chem. 2005 Dec;24(12):3053-60. doi: 10.1897/05-110r.1.

Abstract

Stress and immune function are linked in all vertebrates, including teleost fish. Polychlorinated biphenyls (PCBs) are immunotoxic and impair the ability of fish to respond to additional stressors. In this study, we investigated the effects of PCB126 on stress and immune function and the interaction of these systems in fish using primary cultures of rainbow trout anterior kidney cells as a model. Gene expression levels of cytochrome P4501A (CYP1A), interleukin-1beta (IL-1beta), and glucocorticoid receptor (GR) were measured by real-time quantitative polymerase chain reaction. These genes play important roles in detoxification and immune and stress homeostasis, respectively. Incubation with PCB126 led to increased IL-1beta expression between 30 min and 2 h of exposure, with expression back to basal levels after 6 h. Lipopolysaccharide (LPS) incubation evoked normal IL-1beta responses after 2 and 24 h PCB incubation. Gene expression levels of GR and CYP1A increased in a time- and dose-dependent manner, reaching a plateau after 12 h of incubation. Preincubation with cortisol resulted in decreased IL-1beta expression, increased expression of CYP1A and GR, and was accompanied by an abolished PCB responsiveness after more than 4 h of cortisol incubation. We conclude that PCB126 exposure is not "stressful," as increased cortisol levels would result in depressed IL-1beta expression. Incubation with PCB126 evokes a transient stimulation rather than permanent damage of the immune system, as LPS stimulation resulted in increased IL-1beta expression after PCB incubation. Prolonged cortisol preincubation, resembling a chronic stress paradigm, negatively affects the immune responsiveness of the cells as well as their capacity for toxicant metabolization.

摘要

压力与免疫功能在包括硬骨鱼在内的所有脊椎动物中都存在关联。多氯联苯(PCBs)具有免疫毒性,会损害鱼类对其他应激源作出反应的能力。在本研究中,我们以虹鳟鱼前肾细胞的原代培养物为模型,研究了多氯联苯126(PCB126)对鱼类压力和免疫功能以及这些系统之间相互作用的影响。通过实时定量聚合酶链反应测量细胞色素P4501A(CYP1A)、白细胞介素-1β(IL-1β)和糖皮质激素受体(GR)的基因表达水平。这些基因分别在解毒、免疫和压力稳态中发挥重要作用。用PCB126孵育导致暴露30分钟至2小时之间IL-1β表达增加,6小时后表达恢复到基础水平。在PCB孵育2小时和24小时后,脂多糖(LPS)孵育引发正常的IL-1β反应。GR和CYP1A的基因表达水平以时间和剂量依赖的方式增加,孵育12小时后达到平台期。用皮质醇预孵育导致IL-1β表达降低、CYP1A和GR表达增加,并且在皮质醇孵育超过4小时后伴随着PCB反应性的消失。我们得出结论,暴露于PCB126并非“有压力的”,因为皮质醇水平升高会导致IL-1β表达降低。用PCB126孵育引发的是免疫系统的短暂刺激而非永久性损伤,因为在PCB孵育后LPS刺激导致IL-1β表达增加。类似于慢性应激模式的长时间皮质醇预孵育会对细胞的免疫反应性及其对毒物代谢的能力产生负面影响。

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