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Thyrotropin-Mediated Repression of Class II Trans-Activator Expression in Thyroid Cells: Involvement of STAT3 and Suppressor of Cytokine Signaling
- Source :
- The Journal of Immunology. 171:616-627
- Publication Year :
- 2003
- Publisher :
- The American Association of Immunologists, 2003.
-
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.
- Subjects :
- endocrine system diseases
medicine.medical_treatment
Thyroid Gland
Thyrotropin
Suppressor of Cytokine Signaling Proteins
Mice
Histocompatibility Antigens
Immunology and Allergy
STAT1
SOCS3
Promoter Regions, Genetic
STAT3
Cells, Cultured
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Interferon-Stimulated Gene Factor 3
DNA-Binding Proteins
Cytokine
hormones, hormone substitutes, and hormone antagonists
Protein Binding
Signal Transduction
STAT3 Transcription Factor
endocrine system
Immunology
Down-Regulation
chemical and pharmacologic phenomena
Biology
Response Elements
Transfection
Major histocompatibility complex
Cell Line
Interferon-gamma
Suppressor of Cytokine Signaling 1 Protein
CIITA
medicine
Animals
Humans
MHC class II
Suppressor of cytokine signaling 1
Proteins
Phosphoproteins
Rats
Repressor Proteins
Suppressor of Cytokine Signaling 3 Protein
Protein Biosynthesis
Trans-Activators
biology.protein
Cancer research
Cattle
Carrier Proteins
Interferon Regulatory Factor-1
Transcription Factors
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 171
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....b05589e745577e345ad8cac8907d42db