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. 1992 Mar 1;89(5):1944–1948. doi: 10.1073/pnas.89.5.1944

Hormonal regulation of major histocompatibility complex class I genes in rat thyroid FRTL-5 cells: thyroid-stimulating hormone induces a cAMP-mediated decrease in class I expression.

M Saji 1, J Moriarty 1, T Ban 1, L D Kohn 1, D S Singer 1
PMCID: PMC48570  PMID: 1311856

Abstract

Thyrocytes normally express major histocompatibility complex (MHC) class I, but not class II, cell surface antigens. A rat thyrocyte cell line, FRTL-5, also expresses MHC class I antigens, in addition to a variety of thyroid-specific genes. Treatment of FRTL-5 thyrocytes with physiological concentrations of thyroid-stimulating hormone (TSH) has been shown to induce increased expressed of thyroglobulin and thyroid peroxidase but to simultaneously decrease expression of the TSH receptor. The reduction in TSH receptor expression by TSH is cAMP mediated. In the present study, it is demonstrated that, in thyrocytes treated with TSH, MHC class I expression decreases concomitant with the decrease in TSH receptor expression. This decreased expression is evidenced by reduced cell surface levels of MHC class I antigens, by reduced steady-state RNA levels, and by reduced transcription of the class I genes. TSH-mediated reduction of MHC class I gene transcription in FRTL-5 cells was mapped to a region within 135 base pairs of the promoter.

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Selected References

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  1. Akamizu T., Ikuyama S., Saji M., Kosugi S., Kozak C., McBride O. W., Kohn L. D. Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5677–5681. doi: 10.1073/pnas.87.15.5677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ambesi-Impiombato F. S., Coon H. G. Thyroid cells in culture. Int Rev Cytol Suppl. 1979;(10):163–172. doi: 10.1016/s0074-7696(08)60619-1. [DOI] [PubMed] [Google Scholar]
  3. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bottazzo G. F., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983 Nov 12;2(8359):1115–1119. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
  5. Burman K. D., Baker J. R., Jr Immune mechanisms in Graves' disease. Endocr Rev. 1985 Spring;6(2):183–232. doi: 10.1210/edrv-6-2-183. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Cosman D., Khoury G., Jay G. Three classes of mouse H-2 messenger RNA distinguished by analysis of cDNA clones. Nature. 1982 Jan 7;295(5844):73–76. doi: 10.1038/295073a0. [DOI] [PubMed] [Google Scholar]
  8. Ehrlich R., Sharrow S. O., Maguire J. E., Singer D. S. Expression of a class I MHC transgene: effects of in vivo alpha/beta-interferon treatment. Immunogenetics. 1989;30(1):18–26. doi: 10.1007/BF02421465. [DOI] [PubMed] [Google Scholar]
  9. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R. C., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet. 1983 Nov 12;2(8359):1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
  12. Isozaki O., Kohn L. D., Kozak C. A., Kimura S. Thyroid peroxidase: rat cDNA sequence, chromosomal localization in mouse, and regulation of gene expression by comparison to thyroglobulin in rat FRTL-5 cells. Mol Endocrinol. 1989 Nov;3(11):1681–1692. doi: 10.1210/mend-3-11-1681. [DOI] [PubMed] [Google Scholar]
  13. Israël A., Le Bail O., Hatat D., Piette J., Kieran M., Logeat F., Wallach D., Fellous M., Kourilsky P. TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors. EMBO J. 1989 Dec 1;8(12):3793–3800. doi: 10.1002/j.1460-2075.1989.tb08556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neufeld D. S., Davies T. F. Detection and regulation of rat thyroid MHC class II (RT1.D) transcripts. Mol Endocrinol. 1988 Jun;2(6):507–511. doi: 10.1210/mend-2-6-507. [DOI] [PubMed] [Google Scholar]
  16. Neufeld D. S., Platzer M., Davies T. F. Reovirus induction of MHC class II antigen in rat thyroid cells. Endocrinology. 1989 Jan;124(1):543–545. doi: 10.1210/endo-124-1-543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Piccinini L. A., Roman S. H., Davies T. F. Autoimmune thyroid disease and thyroid cell class II major histocompatibility complex antigens. Clin Endocrinol (Oxf) 1987 Feb;26(2):253–272. doi: 10.1111/j.1365-2265.1987.tb00783.x. [DOI] [PubMed] [Google Scholar]
  18. Platzer M., Neufeld D. S., piccinini L. A., Davies T. F. Induction of rat thyroid cell MHC class II antigen by thyrotropin and gamma-interferon. Endocrinology. 1987 Dec;121(6):2087–2092. doi: 10.1210/endo-121-6-2087. [DOI] [PubMed] [Google Scholar]
  19. Saji M., Akamizu T., Sanchez M., Obici S., Avvedimento E., Gottesman M. E., Kohn L. D. Regulation of thyrotropin receptor gene expression in rat FRTL-5 thyroid cells. Endocrinology. 1992 Jan;130(1):520–533. doi: 10.1210/endo.130.1.1309347. [DOI] [PubMed] [Google Scholar]
  20. Saji M., Ikuyama S., Akamizu T., Kohn L. D. Increases in cytosolic Ca++ down regulate thyrotropin receptor gene expression by a mechanism different from the cAMP signal. Biochem Biophys Res Commun. 1991 Apr 15;176(1):94–101. doi: 10.1016/0006-291x(91)90894-d. [DOI] [PubMed] [Google Scholar]
  21. Santisteban P., Kohn L. D., Di Lauro R. Thyroglobulin gene expression is regulated by insulin and insulin-like growth factor I, as well as thyrotropin, in FRTL-5 thyroid cells. J Biol Chem. 1987 Mar 25;262(9):4048–4052. [PubMed] [Google Scholar]
  22. Todd I., Londei M., Pujol-Borrell R., Mirakian R., Feldmann M., Bottazzo G. F. HLA-D/DR expression on epithelial cells: the finger on the trigger? Ann N Y Acad Sci. 1986;475:241–250. doi: 10.1111/j.1749-6632.1986.tb20873.x. [DOI] [PubMed] [Google Scholar]
  23. Todd I., Pujol-Borrell R., Hammond L. J., Bottazzo G. F., Feldmann M. Interferon-gamma induces HLA-DR expression by thyroid epithelium. Clin Exp Immunol. 1985 Aug;61(2):265–273. [PMC free article] [PubMed] [Google Scholar]
  24. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]

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