DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells

Abstract

Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2 0 ,4,4 0 ,5,5 0 -hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 mg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression ''in vitro'' in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNF induced by DDE and PCB 153 and was independent of AhR activation.

Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells

“…In addition, AhR and non-AhR effects are difficult to separate on gene-level. One study found that DDE and PCB 153 up-regulated expression of AhR mRNA independent of direct AhR activation [45]. It was suggested that the induction of AhR expression was induced by NF-κB which promotes an inflammatory loop, via pro-inflammatory cytokines expression as interleukin (IL)-1 β and TNFα [46].…”

Bioaccumulation of PCBs, OCPs and PBDEs in Marine Mammals From West Antarctica

“…Gene transcription of aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor (AHR) and peroxisome proliferator-activated receptor alpha (PPARα) showed significant relationships with HCB, chlordanes, DDTs, 29 PCBs, and PCB homologs groups, but not with PBDEs and 3-Cl biphenyls. AHR and ARNT are induced by environmental contaminants and mediate immunotoxic compounds (Gaspar-Ramírez et al, 2015). AHR, ARNT and PPARα transcription were previously found to be associated with the exposure to organic pollutants in Baikal seals (Kim et al, 2005;Ishibashi et al, 2008) and in harbor seals (Lehnert et al, 2016).…”