title: Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling.
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-gamma have a significantly higher level of cell surface rat MHC class II RTI.B. However, the IFN-gamma-induced RT1.B expression was suppressed significantly in cells incubated in the presence of thyrotropin. Thyrotropin (TSH) represses IFN-gamma-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-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. However, TSH repression of the IFN-gamma-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.
authors.affiliation: Laboratory of Endocrine Cell Biology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejon, Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
authors.forename: Jae Mi
authors.initials: JM
authors.lastname: Suh
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Hwang
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Hyo Kyun
authors.initials: HK
authors.lastname: Chung
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Song
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Hwang
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Ro
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Chang
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Kohn
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012097:Repressor Proteins; D020218:Response Elements / Q000276:immunology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013972:Thyrotropin / Q000502:physiology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006649:Histocompatibility Antigens; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D047908:Intracellular Signaling Peptides and Proteins; C494258:Irf1 protein, mouse; C494259:Irf1 protein, rat; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C491590:Socs1 protein, mouse; C491589:Socs1 protein, rat; C491411:Socs3 protein, mouse; C491410:Socs3 protein, rat; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C079868:gamma interferon activation factor; C038353:histocompatibility antigens RT, rat; D007371:Interferon-gamma; D013972:Thyrotropin