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Title 

Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling

Authors 

H KimJ M SuhE S HwangD W KimH K ChungJ H SongJung Hwan HwangK C ParkH K RoE K JoJ S ChangTae Hoon LeeM S LeeL D KohnM H Shong

Publisher 

American Association of Immunologists

Issue Date 

2003

Citation 

Journal of Immunology, vol. 171, no. 2, pp. 616-627

Keywords 

cytokinemajor histocompatibility antigen class 1major histocompatibility antigen class 2major histocompatibility class II transactivatorSTAT3 proteinSTAT3 S727A proteinSTAT3 Y705F proteinsuppressor of cytokine signaling 1suppressor of cytokine signaling 3thyrotropin

Abstract 

It has been suggested that class I and class II MHC are contributing factors for numerous diseases including autoimmune thyroid diseases, type 1 diabetes, rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis. The class II trans-activator (CIITA), which is a non-DNA-binding regulator of class II MHC transcription, regulates the constitutive and inducible expression of the class I and class II genes. FRTL-5 thyroid cells incubated in the presence of IFN-γ have a significantly higher level of cell surface rat MHC class II RTI.B. However, the IFN-γ-induced RT1.B expression was suppressed significantly in cells incubated in the presence of thyrotropin. Thyrotropin (TSH) represses IFN-γ-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-γ and also exhibited TSH repression of the IFN-γ-mediated induction of CIITA. However, TSH repression of the IFN-γ-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. This report suggests that TSH is also engaged in immunomodulation through signal cross-talk with the cytokines in thyroid cells.

ISSN 

0022-1767

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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