DEHP induces immunosuppression through disturbing inflammatory factors and CYPs system homeostasis in common carp neutrophils

Abstract

Di-(2-ethylhexyl) phthalate (DEHP), a common pollutant in the water environment, has been reported to be associated with immune functions, especially aquatic organisms. However, whether DEHP exposure causes neutrophils toxicity in common carp is still unclear. To investigate the toxic effect of DEHP on immune functions, common carp neutrophils were exposed to DEHP (40 μmol/L and 200 μmol/L) for 2 h. The common carp neutrophils exposed to DEHP showed a decrease in neutrophil phagocytosis rate compared with control group. DEHP exposure induced a significant decrease in mRNA expression levels of inflammatory cytokines-related genes (Interleukin-6, Interleukin-8, transforming growth factor, tumor necrosis factor (TNF)-α, TNF-R1, TNF-T1, Interferon (IFN)-2a, IFN-g2b, IFN-g1) in common carp neutrophils, while the expression levels of IL-1β and IL-10 were increased compared with control group (P < 0.05). Furthermore, the detection of cytochrome P450 enzyme related genes showed that the mRNA expression levels of CYP (cytochrome P450 proteins)-1A, CYP-1B1, CYP-C1, CYP-2K were significantly decreased, and the mRNA expression level of CYP-3A was significantly reduced (P < 0.05). The results indicated that DEHP could affect the phagocytic ability of neutrophils by regulating the expression of inflammatory cytokines and disrupting cytochrome P450 homeostasis, which caused the immunosuppression in common carp.