Endocrine Abstracts

Objective: Polychlorinated biphenyls (PCBs) are persistent organic pollutants that that have been reported to cause a variety of toxic effects, including inflammation and cancer, through binding to the aryl hydrocarbon receptor (AhR). In turn, AhR promotes xenobiotic detoxification and antioxidant defense, by up-regulating specific responsive genes, the so-called “AhR gene battery”. AhR is also involved in modulation of immune response, by regulating programmed cell death 1(PD-1) ligand (PD-L1) levels. PD-L1 has an important role in regulating immune responses by binding to PD-1 on immune cells, contributes to maintaining immune tolerance by down-regulating of T-cell immune responses and cytokine production, and might favor the escape from immune surveillance of cancer cells. The aim of this study is to investigate the effects of PCBs on PD-L1 expression on thyroid cells

Methods: Primary thyrocytes were obtained from patients undergone surgery for benign thyroid disease (solitary thyroid nodule). Cultured cells were exposed for 24 h to increasing concentrations (2.5 and 5 µM) of 2 dioxin-like PCBs: the 2,3’,4,4’,5-pentachlorobiphenyl (PCB 118) and the 3,3’,4’,4’,5 Pentachlorobiphenyl (PCB 126). Gene silencing of AhR was performed by using a specific siRNA. mRNA and protein levels of PD-L1, AhR, IL-1beta and IL-6 were evaluated by real-time qPCR, ELISA and Western Blot.

Results: In cultured thyrocytes, exposure to PCB 126 and PCB 118 at 2.5 and 5 µM concentrations significantly induced the increase of both mRNA and protein levels of AhR and PD-L1 (P < 0.01 and P < 0.001, at 2.5 and 5 µM respectively for mRNA expression and P < 0.05 at 5 µM for protein levels). On the contrary, the knockdown of AhR before PCBs treatments reduced PD-L1 mRNA and related protein levels, indicating the involvement of this receptor in the regulation of PD-L1 enhanced by PCBs. In the same in vitro model, PCB exposure induced the increase of both mRNA and protein levels of inflammatory cytokines IL-1beta and IL-6 (P < 0.01 and P < 0.001, at 5 and 10 µM respectively for mRNA expression; P < 0.05 and P < 0.01 at 5 and 10 µM for protein levels).

Conclusion: Our data demonstrated that PCB 118 and PCB 126 may promote PD-L1 expression in thyrocytes. Such effects can be partially attributed to the activation of the AhR. These results suggest that the PD-1/PD-1L pathway is activated in thyrocytes in the context of inflammatory/toxic stimuli and point to a new mechanism that need to be further deepen to understand the effect of PCBs on thyrocytes.