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- W4244618387 abstract "TSH is known as an important hormone that plays the major role not only in the maintenance of normal physiology but also in the regulation of immunomodulatory gene expression in thyrocytes. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1) was identified as one of the proteins that are abnormally expressed in the thyroid gland during autoimmune thyroid diseases. In this study we found that TSH inhibits interferon-γ (IFNγ)-mediated expression of the ICAM-1 gene, and we investigated the involved mechanisms in rat FRTL-5 thyroid cells. After exposure to IFNγ, ICAM-1 expression is positively regulated at the level of transcription. This effect occurs via the IFNγ-activated site (GAS) element in the ICAM-1 promoter as a consequence of the activation of STAT1 (signal transducer and activator of transcription-1), but not of STAT3. On the other hand, after exposure to TSH plus IFNγ, ICAM-1 transcription is negatively modulated. We found that this inhibitory effect of TSH also occurs via the GAS element. Electrophoretic mobility shift assays confirmed that the IFNγ-induced DNA-binding activities of STAT1 were reduced by TSH. Furthermore, our results showed that the inhibitory effect of TSH on IFNγ signaling is caused by inhibition of tyrosine phosphorylation on STAT1, Janus kinase-1 (Jak1), and IFNγ receptor α, but not Jak2. In conclusion, we have identified a novel mechanism in which TSH modulates the IFNγ-mediated Jak/STAT signaling pathway through the inhibition of Jak1 and STAT1." @default.
- W4244618387 created "2022-05-12" @default.
- W4244618387 creator A5088198759 @default.
- W4244618387 date "2000-06-01" @default.
- W4244618387 modified "2023-09-23" @default.
- W4244618387 title "Thyrotropin Modulates Interferon- -Mediated Intercellular Adhesion Molecule-1 Gene Expression by Inhibiting Janus Kinase-1 and Signal Transducer and Activator of Transcription-1 Activation in Thyroid Cells" @default.
- W4244618387 doi "https://doi.org/10.1210/en.141.6.2090" @default.
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