2, 3′, 4, 4′, 5- Pentachlorobiphenyl Induces Inflammatory Responses in Thyroid through a JNK and Aryl Hydrocardon Receptor Mediated Pathway
Polychlorinated biphenyls (PCBs) are persistent and widely distributed environmental pollutants that can compromise normal functions of multiple organs and systems, one important mechanism is the induction of inflammatory disorders. In this study, we investigated the effects of 2, 3′, 4, 4′, 5- Pentachlorobiphenyl (PCB118) on inflammatory responses and the underlying mechanisms in thyroid. Wistar rats were dosed with PCB118 intraperitoneally at 0, 10, 100 and 1000 ‘g/kg/day, 5 days per week for 13 weeks; rat thyroid FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5, 25 nM) for indicated times. Results showed that PCB118 promoted the expression of interleukin-6 (IL-6), tumor necrosis factor-‘ (TNF-‘) and intercellular adhesion molecule-1 (ICAM-1) in time- and dose-dependent manner and decreased sodium/iodide symporter (NIS) protein. In vivo and in vitro studies also indicated that JNK pathway was activated after PCB118 exposure, and the experiments using small interfering RNA for JNK partially blocked PCB118’induced upregulation of IL-6 and ICAM-1, and downregulation of NIS. Moreover, pretreatment of thyroid cells with the aryl hydrocardon receptor (AhR) inhibitor ‘-naphthflavone (‘-NF) suppressed IL-6 and ICAM-1 and restored NIS expression. Taken together, PCB118 stimulates expression and secretion of IL-6, TNF-‘ and ICAM-1 in thyroid through activation of AhR and JNK, and subsequently interferes with NIS expression, resulting in disruption of the thyroid structure and function.
Polychlorinated biphenyls 118; JNK pathway; IL-6, TNF-‘, ICAM-1; AhR; sodium iodide symporter; thyroid inflammation
Polychlorinated biphenyls (PCBs) are ubiquitous synthetic organic pollutants that contaminate the environment. Due to their high lipophilicity and chemical stability, they are widely existed, and may biomagnify through the food chain and bioaccumulate in organisms. PCBs cause a variety of toxic effects, affecting immune, endocrine, nervous and reproductive system (Arnold et al. 1995; Golden and Kimbrough 2009; Portigal et al. 2002; Zhao et al. 2009). The majority of toxic effects elicited by coplanar PCBs are mediated by its binding to the aryl hydrocardon receptor (AhR), and subsequent induction of responsive genes (Barouki et al. 2007; Puga et al. 2009). In addition, one of the important mechanisms of PCBs toxicity is inflammation (Hennig et al. 2002; Imbeault et al. 2012; Kim et al. 2012). PCBs can induce inflammation in multiple systems and promote inflammatory cytokine levels such as interleukin-6 (IL-6), tumor necrosis factor-‘ (TNF-‘) and intercellular adhesion molecule-1 (ICAM-1) (Hayley et al. 2011; Koike et al. 2014).
Importantly, the thyroid axis appears to be susceptible to the influence of PCBs (Murk et al. 2013), and recent concerns have mainly focused on their thyroid hormone disturbance effects. Our early findings suggested that low concentrations of 2,3′,4,4’,5-pentachlorobiphenyl, or polychlorinated biphenyl 118 (PCB118), could disrupt thyroid structure, interfering with thyroid hormone and decreasing the pivotal gene expressions of sodium/iodide symporter (NIS) and thyroglobulin (TG) both in PCB118 treated rats and in cultured primary human thyroid cells (Guo et al. 2015; Tang et al. 2013a). However, it is not known whether inflammation would play …
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