ECE2022 Poster Presentations Environmental Endocrinology (11 abstracts)
Dioxin-like polychlorinated biphenyl (pcbs) congeners induce inflammatory responses and reduce thyroid-specific genes expression in human thyrocytes via ahr pathways
Rosaria Ruggeri 1,2 , Aurelio Minuti 2,3 , Federica Aliquò 2,3 , Fiorenza Gianì 4 , Roberta Masto 4 , Davide Romano 3 , Angela Avenoso 3 , Maria Teresa Cristani 5 , Francesco Trimarchi 1 , Alfredo Campennì 3 , Angela D’Ascola 1 & Salvatore Cannavò 2,6
1University of Messina, Dept Clinical and Experimental Medicine, Messina, Italy; 2Endocrine Unit, University Hospital G. Martino, Messina, Italy; 3Dept Biomedical and Dental Sciences, and Morpho-Functional Images, University of Messina, Messina, Italy; 4University of Catania, Dept Clinical and Experimental Medicine, Catania, Italy; 5University of Messina, Chemical, Biological, Pharmaceutical and Environmental Sciences, Messina, Italy; 6University of Messina, Department of Human Pathology of Adulthood and Childhood DETEV, Messina, Italy
Background: PCBs are persistent organic pollutants, able to affect thyroid function (endocrine disruptors) and promote inflammation through multiple mechanisms. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor able to bind dioxins and dioxin-like pollutants including PCBs, play a key role in xenobiotic response, by up-regulating specific responsive genes, the so-called “AhR gene battery”, including cytochrome P450 1A1 (CYP1A1) and Nuclear factor-2 erythroid related factor-2 (Nrf2), a master regulator of the redox homeostasis with simultaneous anti-inflammatory activity. Aim of the present study was to investigate the influences of the AhR agonist PCBs congeners on thyrocytes in vitro.
Methods: Cultured primary thyrocytes were exposed for 24 h to increasing concentrations (5 and 10 μM) of 2.3’,4.4’,5-pentachlorobiphenyl (PCB 118) and 3.3’,4’,4’,5 Pentachlorobiphenyl (PCB 126). mRNA and proteins expression for IL-1β IL-6, NIS, TG, AHR, CYP1A1 and Nrf2 were evaluated by real-time PCR and Western Blot and ELISA, respectively. Protein quantification was assessed by densitometry analysis
Results: In cultured thyrocytes, exposure to PCB 126 and PCB 118 at 5 and 10 μM concentrations significantly induced the increase of both mRNA and protein levels of the 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). Additionally, both mRNA and protein levels of the AhR and the downstream molecules CYP1A1 and NRF2 were increased in PCBs-treated thyrocytes (for AhR and Nrf2 P<0.05 at highest concentration; for CYP1A1 P<0.05 and P<0.01 at 5 and 10 μM respectively), suggesting activation of AhR pathways and oxidative stress sensitive markers (CYP1A1and NRF2) induction in response to PCBs exposure. On the contrary, the levels of Tg and NIS mRNA and related protein decreased after PCBs treatments at 5 and 10 μM concentrations (P<0.05 and P<0.01, for mRNA expression at 5 and 10 μM respectively; P<0.05 at 10 μM for protein levels), indicating down-regulation of these thyroid-specific genes in PCBs-induced inflammation.
Conclsion: PCB 118 and PCB 126 may promote inflammatory responses, leading to alteration in Tg and NIS genes expression in thyrocytes. Such effects can be partially attributed to the activation of the AhR that, in turn, induces CYP1A1 and NRF2, causing changes in the cellular redox status. These data may contribute to explain the mechanisms underlying thyroid toxicity of dioxin-like PCBs and highlight the potential role of these environmental pollutants in contributing to autoimmune thyroid inflammation and damage.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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