Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells

Suzuki, Koichi; Kimura, Hiroaki; Wu, Huhehasi; Kudo, Naoko; Kim, Won; Suzuki, Shingo; Yoshïda, Akio; Caturegli, Patrizio; Kohn, Leonard D.

doi:10.1016/j.bbrc.2010.01.123

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…As previously reported, SLC5A5 expression was significantly suppressed by increasing concentrations of iodide (Fig. 5A) (27,31,39). The ability of iodide to decrease Slc5a5 expression was inhibited by perchlorate as seen in FRTL-5 cells (Supplementary Fig.…”

Section: Innate Immune Activation Of the Thyroid Is Induced By Iodidesupporting

confidence: 82%

Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions

Kawashima

Yamazaki²,

Hara

et al. 2013

Thyroid

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Background: Autoimmune thyroid disease is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. However, the underlying mechanisms by which specific thyroid antibodies are produced are largely unknown. Recent studies have shown that innate immune responses affect both the phenotype and the severity of autoimmune reactions. Moreover, it appears that even non-immune cells, including thyroid cells, have an ability to launch such responses. The aim of this study was to conduct a more detailed analysis of innate immune responses of the thyroid upon stimulation with various ''non-self'' and ''self'' factors that might contribute to the initiation of autoimmune reactions. Methods: We used rat thyroid FRTL-5 cells, human thyroid cells, and mice to investigate the effects of various pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and iodide on gene expression and function that were related to innate immune responses. Results: RT-PCR analysis showed that both rat and human thyroid cells expressed mRNAs for Toll-like receptors (TLRs) that sense PAMPs. Stimulation of thyrocytes with TLR ligands resulted in activation of the interferon-beta (IFN-b) promoter and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFjB)-dependent promoter. As a result, pro-inflammatory cytokines, chemokines, and type I interferons were produced. Similar activation was observed when thyroid cells were stimulated with double-stranded DNA, one of the typical DAMPs. In addition to these PAMPs and DAMPs, treatment of thyroid cells with high concentrations of iodide increased mRNA expression of various cytokines. Conclusion: We show that thyroid cells express functional sensors for exogenous and endogenous dangers, and that they are capable of launching innate immune responses without the assistance of immune cells. Such responses may relate to the development of thyroiditis, which in turn may trigger autoimmune reactions.

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Section: Innate Immune Activation Of the Thyroid Is Induced By Iodidesupporting

confidence: 82%

Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions

Kawashima

Yamazaki²,

Hara

et al. 2013

Thyroid

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“…Our results support and extend these data by demonstrating that the decrease in NIS mRNA does not take place at the transcriptional level. This result is also in agreement with recent data showing I Ϫ effects on NIS mRNA stabilization (23) but is in contradiction to the findings of other authors who used higher I Ϫ doses (10 mM) (32). Furthermore, we found no regulation of Pax8 expression or its …”

Section: Discussionsupporting

confidence: 50%

Regulation of Thyroid Oxidative State by Thioredoxin Reductase Has a Crucial Role in Thyroid Responses to Iodide Excess

Leoni

Kimura

Santisteban

et al. 2011

Molecular Endocrinology

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The phenomenon that supraphysiological doses of iodide (I(-)) temporarily inhibit thyroid hormone synthesis is known as thyroid iodide autoregulation. Recovery of thyroid function has been attributed to sodium-iodide symporter (NIS) inhibition, but the diversity of available data makes it difficult to reach definitive conclusions. Iodide excess induces reactive oxygen species production and cell toxicity. However, the roles of the oxidative state of the cell and antioxidant selenoproteins in I(-) autoregulation have never been explored. Here we analyze the effects of high I(-) doses in rat thyroids and in PCCl3 cells in the period comprising I(-) autoregulation (i.e. 0-72 h after I(-) administration), focusing on NIS expression, redox state, and the expression and activity of selenoproteins. Our results show that NIS mRNA inhibition by I(-) does not occur at the transcriptional level, because neither NIS promoter activity nor Pax8 expression or its binding to DNA was modulated. Because I(-) uptake was inhibited much earlier than NIS protein, and no effect was observed on its subcellular localization, we suggest that I(-) is inhibiting NIS in the plasma membrane. The increased reactive oxygen species production leads to an increase in thioredoxin reductase mRNA levels and enzyme activity, which reduces the oxidative stress. Inhibition of thioredoxin reductase at either gene expression or activity levels prevented NIS recovery, thus illustrating a new role played by this selenoprotein in the regulation of cell homeostasis and consequently in I(-) autoregulation.

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“…Potassium perchlorate is a potent inhibitor of thyroidal iodide uptake [39] and we have shown it to similarly inhibit placental iodide uptake. While there is experimental evidence of low iodide intake resulting in increased NIS expression in an animal model [14], the authors are not aware of any published work implicating high iodide intake downregulating NIS as has been described in the thyroid [38]. Among the pregnancy-associated hormones studied, we have identified in particular hCG, oxytocin and prolactin as the most likely candidates in promoting uptake of iodide by the placenta.…”

Section: Discussionmentioning

confidence: 96%

“…While it is well established that in the thyroid NIS-mediated transport of iodide is driven by the electrochemical sodium gradient generated by the Na(+)/K(+)-ATPase [36], it remains unclear through which pathway 17β-estradiol may act to influence NIS expression [37]. It has been shown that in common with thyroid [38], enhancement of NIS expression and 125 I uptake by retinoids (RA) in lactating breast tissue can be diminished by 17β-estradiol treatment [39], which is in contrast to the positive findings demonstrated by Tazebay et al [20] and in this study, albeit in different tissues. Therefore, it remains unclear through which pathway estrogens may act to influence NIS expression.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Iodide Uptake in Placental Primary Cultures

2013

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Background: Maintenance of adequate iodide supply to the developing fetus is dependent not only on maternal dietary iodine intake but also on placental iodide transport. The objective of this study was to examine the effects of different pregnancy-associated hormones on the uptake of radioiodide by the placenta and to determine if iodide transporter expression is affected by hormone incubation. Methods: Primary cultures of placental trophoblast cells were established from placentas obtained at term from pre-labor caesarean sections. They were pre-incubated with 17β-estradiol, prolactin, oxytocin, human chorionic gonadotropin (hCG) and progesterone either singly or in combination over 12 h with ¹²⁵I uptake being measured after 6 h. RNA was isolated from placental trophoblasts and real-time RT-PCR performed using sodium iodide symporter (NIS) and pendrin (PDS) probes. Results: Significant dose response increments in ¹²⁵I uptake by trophoblast cells (p < 0.01) were observed following incubation with hCG (60% increase), oxytocin (45% increase) and prolactin (32% increase). Although progesterone (50-200 ng/ml) and 17β-estradiol (1,000-15,000 pg/ml) alone produced no significant differences in uptake, they facilitated increased uptake when combined with prolactin or oxytocin, with a combination of all four hormones producing the greatest increase (82%). Increased ¹²⁵I uptake was accompanied by corresponding increments in NIS mRNA (ratio 1.52) compared to untreated control cells. No significantly increased expression levels of PDS were observed. Conclusions: Pregnancy-associated hormones, particularly oxytocin and hCG, have a role in promoting placental iodide uptake which may protect the fetus against iodine deficiency.

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Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells

Cited by 25 publications

References 34 publications

Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions

Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions

Regulation of Thyroid Oxidative State by Thioredoxin Reductase Has a Crucial Role in Thyroid Responses to Iodide Excess

Regulation of Iodide Uptake in Placental Primary Cultures

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