Polychlorinated biphenyl 126 affects expression of genes involved in stress-immune interaction in primary cultures of rainbow trout anterior kidney cells.
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.
Quabius
Elgar Susanne
ES
Scottish Fish Immunology Research Centre, University of Aberdeen, Scotland, United Kingdom. e.s.quabius@exeter.ac.uk
Krupp
Guido
G
Secombes
Christopher J
CJ
D000818:Animals; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D006854:Hydrocortisone / Q000378:metabolism; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017686:Oncorhynchus mykiss; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013312:Stress, Physiological / Q000139:chemically induced / Q000276:immunology*; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D006854:Hydrocortisone