Interferon-gamma inhibition of human thyrotropin receptor gene expression.

Nishikawa, T; Yamashita, Shunichi; Namba, Hiroyuki; Usa, Toshiro; Tominaga, Tan; Kimura, Hironori; Izumi, Motomori; Nagataki, Shigenobu

doi:10.1210/jcem.77.4.8408457

Cited by 25 publications

(14 citation statements)

References 37 publications

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“…The inhibition of Tg and cAMP production caused by IFN-was in agreement with other reports where TECs from Graves' patients or fetuses were investigated (Nagayama et al 1987, Huber & Davies 1990, Kung & Lau 1990, Nishikawa et al 1993). However, the inhibitory influence on cAMP production was in contrast with data reported by Kung & Lau (1990) who did not find any change in basal or TSH-stimulated cAMP production.…”

Section: Discussionsupporting

confidence: 91%

Influence of tumour necrosis factor-α, tumour necrosis factor-β and interferon-γ, separately and added together with interleukin-1 β, on the function of cultured human thyroid cells

Rasmussen

Kayser²,

Feldt‐Rasmussen³

et al. 1994

Journal of Endocrinology

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Interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been demonstrated in thyroid tissue. We have previously shown that high concentrations of IL-1 inhibit and low concentrations stimulate human thyroid cell function in vitro. In the present study, TNF-alpha, TNF-beta and IFN-gamma all inhibited thyroglobulin (Tg) and cAMP production from cultured human thyroid cells. When TNF-alpha was added simultaneously with IL-1 beta, the highest concentration of TNF-alpha (10(6) U/l) enhanced the inhibition of Tg and cAMP induced by IL-1 beta (1-10(5) U/l). TNF-beta had no influence on IL-1 beta-induced inhibition. IFN-gamma (10(4) U/l) added together with IL-1 beta in lower concentrations (1-10(2) U/l) stimulated cAMP production, while at high concentrations of IL-1 beta (10(5) U/l), IFN-gamma enhanced the inhibitory influence of IL-1 beta on Tg production. The hormones of the immune system, IL-1, TNF and IFN-gamma, may thus contribute to the decreased thyroid function characteristic of some thyroid inflammatory diseases.

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Section: Discussionsupporting

confidence: 91%

Influence of tumour necrosis factor-α, tumour necrosis factor-β and interferon-γ, separately and added together with interleukin-1 β, on the function of cultured human thyroid cells

Rasmussen

Kayser²,

Feldt‐Rasmussen³

et al. 1994

Journal of Endocrinology

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“…IFNg is a cytokine that is mainly involved in anti-viral and anti-bacterial responses and is produced by natural killer and T-cells. INFg has a variety of effects on human thyrocytes in culture; it inhibits TSH-induced TH and Tg secretion (Nagayama et al 1987, Kung et al 1992 as well as Tg mRNA expression (Sato et al 1990), TSH-induced TPO expression ) and the TSH-and cAMPinduced upregulation of TSH receptors on the thyrocyte (Nishikawa et al 1993). IFNg also inhibits the TSH-induced increase in NIS expression in rat FTRL-5 cells resulting in diminished iodide uptake (Ajjan et al 1998).…”

Section: The Effect Of Cytokines On Th Synthesismentioning

confidence: 99%

The molecular basis of the non-thyroidal illness syndrome

Vries¹,

Fliers²,

Boelen³

2015

Journal of Endocrinology

152

116

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The 'sick euthyroid syndrome' or 'non-thyroidal illness syndrome' (NTIS) occurs in a large proportion of hospitalized patients and comprises a variety of alterations in the hypothalamus-pituitary-thyroid (HPT) axis that are observed during illness. One of the hallmarks of NTIS is decreased thyroid hormone (TH) serum concentrations, often viewed as an adaptive mechanism to save energy. Downregulation of hypophysiotropic TRH neurons in the paraventricular nucleus of the hypothalamus and of TSH production in the pituitary gland points to disturbed negative feedback regulation during illness. In addition to these alterations in the central component of the HPT axis, changes in TH metabolism occur in a variety of TH target tissues during NTIS, dependent on the timing, nature and severity of the illness. Cytokines, released during illness, are known to affect a variety of genes involved in TH metabolism and are therefore considered a major determinant of NTIS. The availability of in vivo and in vitro models for NTIS has elucidated part of the mechanisms involved in the sometimes paradoxical changes in the HPT axis and TH responsive tissues. However, the pathogenesis of NTIS is still incompletely understood. This review focusses on the molecular mechanisms involved in the tissue changes in TH metabolism and discusses the gaps that still require further research.

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“…Administration of TNF␣ to human or rodents results in decreased serum thyroid hormone concentrations, iodide uptake and TSH-induced T3 and T4 release [Ozawa et al, 1988;Pang et al, 1989;van der Poll et al, 1990]. In human thyroid cells, IFN␥ blocks TSH-induced increases in TSH receptor (TSHR) content and mRNA levels, thyroid peroxidase (TPO), and thyroglobulin (Tg) [Nishikawa et al, 1993;Asakawa et al, 1992;Kung and Lau, 1990]. Further, IFN␥ and TNF␣ decrease TSH-induced iodide uptake and release of T3 and T4 into the medium by human thyrocytes [Sato et al, 1990].…”

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confidence: 99%

Induction of transcription factor interferon regulatory factor-1 by interferon-? (IFN?) and tumor necrosis factor-? (TNF?) in FRTL-5 cells

et al. 1999

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While it is well known that interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) play a role in the regulation of thyroid growth and differentiated functions, the cellular and molecular mechanisms involved in mediating the effects of IFN gamma and TNF alpha on thyroid function are unknown. In the present study, we used FRTL-5 rat thyroid cells to examine the effects of IFN gamma and TNF alpha on gene expression of transcription factor interferon regulatory factor-1 (IRF-1), which is involved in mediating the effects of these cytokines in a number of cell types. Northern blot analysis of FRTL-5 mRNA showed a single IRF-1 mRNA at 2.2 Kb. In quiescent FRTL-5 cells, IRF-1 mRNA levels were low but detectable by Northern analysis. Incubation of FRTL-5 cells with IFN gamma or TNF alpha resulted in a dose- and time-dependent increase in IRF-1 mRNA levels. We have shown that TNF-alpha and IFN-gamma act synergistically to block the TSH-induced increase in type I 5'-deiodinase(5'D-I) activity and 5'D-I gene expression in FRTL-5 rat thyroid cells. Incubation of FRTL-5 cells with IFN gamma and TNF alpha in combination, however, did not synergistically increase IRF-1 mRNA levels. Electrophoretic mobility shift assay (EMSA) revealed that IFN gamma induced the formation of a single complex to a IFN gamma activation site (GAS) probe in a dose dependent manner. Several lines of evidence suggest that TNF alpha activates transcription factor nuclear factor-kappa B (NF kappa B) through activation of protein kinase C (PKC) or the hydrolysis of sphingomyelin to ceramide in a number of cell types. Here we demonstrate that hydrolysis of sphingomyelin to ceramide by sphingomyelinase (SMase), but not activation of PKC by 12-O-tetradecanoylphorbol 13-acetate (TPA), was involved in the activation of NF kappa B in FRTL-5 cells. Similarly, hydrolysis of sphingomyelin to ceramide, but not activation of PKC, resulted in an increased in IRF-1 mRNA levels in FRTL-5 cells. The present data demonstrate that IFN gamma and TNF alpha increase IRF-1 mRNA levels in FRTL-5 cells through activation of GAS and NF kappa B binding proteins, respectively. Thus, our results suggest that upregulation of IRF-1 may play a role in mediating the effects of IFN gamma and TNF alpha on thyroid function. Our results also suggest that the induction of IRF-1 mRNA by IFN gamma and TNF alpha is not the cellular mechanism involved in the synergistic effect of these cytokines on thyroid function.

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Interferon-gamma inhibition of human thyrotropin receptor gene expression.

Cited by 25 publications

References 37 publications

Influence of tumour necrosis factor-α, tumour necrosis factor-β and interferon-γ, separately and added together with interleukin-1 β, on the function of cultured human thyroid cells

Influence of tumour necrosis factor-α, tumour necrosis factor-β and interferon-γ, separately and added together with interleukin-1 β, on the function of cultured human thyroid cells

The molecular basis of the non-thyroidal illness syndrome

Induction of transcription factor interferon regulatory factor-1 by interferon-? (IFN?) and tumor necrosis factor-? (TNF?) in FRTL-5 cells

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