title: 2,3',4,4',5-Pentachlorobiphenyl Induces Inflammatory Responses in the Thyroid Through JNK and Aryl Hydrocarbon Receptor-Mediated Pathway.
abstract: Polychlorinated biphenyls (PCBs) are durable and widely distributed environmental contaminants that can compromise the normal functions of multiple organs and systems; one important mechanism is the induction of inflammatory disorders. In this study, we explored the influences of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on inflammatory responses and its underlying mechanisms in the thyroid. Wistar rats were administered PCB118 intraperitoneally at 0, 10, 100, and 1000 μg/kg/d, 5 days a week for 13 weeks; rat thyroid FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5, and 25 nM) for indicated time. Results revealed that PCB118 promoted the generation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in a time- and dose-related manner and decreased sodium/iodide symporter (NIS) protein expression. Moreover, stimulation with PCB118 resulted in the upregulation of the aryl hydrocarbon receptor (AhR)-responsive gene cytochrome P450 1A1 in FRTL-5 cells; whereas pretreatment with the AhR inhibitor α-naphthoflavone or AhR small interfering RNA (siRNA) suppressed AhR, CYP1A1, IL-6, and ICAM-1 and restored NIS expression. In vivo and in vitro studies also suggested that the c-Jun N-terminal kinase (JNK) pathway was activated on PCB118 exposure, and the experiments using siRNA for JNK partially blocked PCB118-induced upregulation of IL-6 and ICAM-1 and downregulation of NIS. Altogether, PCB118 stimulates production of IL-6, TNF-α, and ICAM-1 in the thyroid through AhR and JNK activations and subsequently interferes with NIS expression, resulting in the disruption of thyroid structure and function.
authors.affiliation: *Department of Endocrinology and.
authors.forename: Bojin
authors.initials: B
authors.lastname: Xu
authors.affiliation: *Department of Endocrinology and.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: *Department of Endocrinology and.
authors.forename: Minne
authors.initials: M
authors.lastname: Sun
authors.affiliation: *Department of Endocrinology and.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: *Department of Endocrinology and.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: *Department of Endocrinology and.
authors.forename: Xuqin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: *Department of Endocrinology and.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: *Department of Endocrinology and.
authors.forename: Dai
authors.initials: D
authors.lastname: Cui
authors.affiliation: *Department of Endocrinology and duanyu@medmail.com.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D018336:Receptors, Aryl Hydrocarbon; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C070055:2,3',4,4',5-pentachlorobiphenyl; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1
keywords: AhR; JNK pathway; inflammatory mediators; polychlorinated biphenyl 118; sodium iodide symporter; thyroid disturbance