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B
Cell Regulation Section (S.-I.T., M.S., C.G., G.N., M.S., V.M., K.S., L.D.K.) Metabolic Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases and Experimental Immunology Branch (D.S.S.) National Cancer Institute National Institutes of Health Bethesda, Maryland 20892
High concentrations of iodide
can induce transient, clinical improvement in patients with autoimmune
Graves’ disease. Previous work has related this iodide action to the
autoregulatory effect of iodide on the growth and function of the
thyroid; more recently, we additionally related this to the ability of
iodide to suppress major histocompatibility (MHC) class I RNA levels
and antigen expression on thyrocytes. In this report, we describe a
transcriptional mechanism involved in iodide suppression of class I
gene expression, which is potentially relevant to the autoregulatory
action of iodide. Transfection experiments in FRTL-5 cells show that
iodide decreases class I promoter activity and that this effect can be
ascribed to the ability of iodide to modulate the formation of two
specific protein/DNA complexes with enhancer A, -180 to -170 bp, of
the class 1 5'-flanking region.1 Thus, iodide decreases the
formation of Mod-1, an enhancer A complex involving the p50 subunit of
NF-
B and a c-fos family member, fra-2, which was
previously shown to be important in the suppression of class I levels
by hydrocortisone. Unlike hydrocortisone, iodide also increases the
formation of a complex with enhancer A, which we show, in antibody
shift experiments, is a heterodimer of the p50 and p65 subunits of
NF-B. The changes in these complexes are not duplicated by chloride
and are related to the action of iodide on class I RNA levels by the
following observations. First, FRTL-5 thyroid cells with an aged
phenotype coincidentally lose the ability of iodide to decrease MHC
class I RNA levels and to induce changes in either complex. Second, the
effect of iodide on class I RNA levels and on enhancer A complex
formation with Mod-1 and the p50/p65 heterodimer is inhibited by agents
that block the inositol phosphate, Ca++,
phospholipase A2, arachidonate signal transduction pathway:
acetylsalicylate, indomethacin, and 5,8,11,14-eicosatetraynoic acid.
Interestingly, iodide can also decrease formation of the Mod-1 complex
and increase formation of the complex with the p50/p65 subunits of
NF-B when the NF-B enhancer sequence from the Ig light chain,
rather than enhancer A, is used as probe; and both actions mimic the
action of a phorbol ester. This suggests that iodide may regulate
complex formation with NF-B regulatory elements on multiple genes
associated with growth and function, providing a potential mechanism
relating the autoregulatory action of iodide on thyroid cells and its
action on class I gene expression.
This article has been cited by other articles:
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  A. S. Kotekar, J. D. Weissman, A. Gegonne, H. Cohen, and D. S. Singer Histone Modifications, but Not Nucleosomal Positioning, Correlate with Major Histocompatibility Complex Class I Promoter Activity in Different Tissues In Vivo Mol. Cell. Biol., December 15, 2008; 28(24): 7323 - 7336. [Abstract] [Full Text] [PDF]
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 C Giuliani, M Saji, I Bucci, G Fiore, M Liberatore, D S Singer, F Monaco, L D Kohn, and G Napolitano Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells. J. Endocrinol., June 1, 2006; 189(3): 605 - 615. [Abstract] [Full Text] [PDF]
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 N. Harii, C. J. Lewis, V. Vasko, K. McCall, U. Benavides-Peralta, X. Sun, M. D. Ringel, M. Saji, C. Giuliani, G. Napolitano, et al. Thyrocytes Express a Functional Toll-Like Receptor 3: Overexpression Can Be Induced by Viral Infection and Reversed by Phenylmethimazole and Is Associated with Hashimoto's Autoimmune Thyroiditis Mol. Endocrinol., May 1, 2005; 19(5): 1231 - 1250. [Abstract] [Full Text] [PDF]
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 T. K. Howcroft, J. D. Weissman, A. Gegonne, and D. S. Singer A T Lymphocyte-Specific Transcription Complex Containing RUNX1 Activates MHC Class I Expression J. Immunol., February 15, 2005; 174(4): 2106 - 2115. [Abstract] [Full Text] [PDF]
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 G. Napolitano, I. Bucci, C. Giuliani, C. Massafra, C. Di Petta, E. Devangelio, D. S. Singer, F. Monaco, and L. D. Kohn High Glucose Levels Increase Major Histocompatibility Complex Class I Gene Expression in Thyroid Cells and Amplify Interferon-{gamma} Action Endocrinology, March 1, 2002; 143(3): 1008 - 1017. [Abstract] [Full Text] [PDF]
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 T. Kimura, A. Van Keymeulen, J. Golstein, A. Fusco, J. E. Dumont, and P. P. Roger Regulation of Thyroid Cell Proliferation by TSH and Other Factors: A Critical Evaluation of in Vitro Models Endocr. Rev., October 1, 2001; 22(5): 631 - 656. [Abstract] [Full Text] [PDF]
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G. Napolitano, V. Montani, C. Giuliani, S. Di Vincenzo, I. Bucci, V. Todisco, G. Laglia, A. Coppa, D. S. Singer, M. Nakazato, et al. Transforming Growth Factor-{beta}1 Down-Regulation of Major Histocompatibility Complex Class I in Thyrocytes: Coordinate Regulation Of Two Separate Elements by Thyroid-Specific as Well as Ubiquitous Transcription Factors Mol. Endocrinol., April 1, 2000; 14(4): 486 - 505. [Abstract] [Full Text]
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 F. Schuppert, D. Ehrenthal, A. Frilling, K. Suzuki, G. Napolitano, and L. D. Kohn Increased Major Histocompatibility Complex (MHC) Expression in Nontoxic Goiters Is Associated with Iodide Depletion, Enhanced Ability of the Follicular Thyroglobulin to Increase MHC Gene Expression, and Thyroid Autoantibodies J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 858 - 867. [Abstract] [Full Text]
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S. Kirshner, L. Palmer, J. Bodor, M. Saji, L. D. Kohn, and D. S. Singer Major Histocompatibility Class I Gene Transcription in Thyrocytes: A Series of Interacting Regulatory DNA Sequence Elements Mediate Thyrotropin/Cyclic Adenosine 3',5'-Monophosphate Repression Mol. Endocrinol., January 1, 2000; 14(1): 82 - 98. [Abstract] [Full Text]
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 H. Kim, T.-H. Lee, E. S. Park, J. M. Suh, S. J. Park, H. K. Chung, O-Y. Kwon, Y. K. Kim, H. K. Ro, and M. Shong Role of Peroxiredoxins in Regulating Intracellular Hydrogen Peroxide and Hydrogen Peroxide-induced Apoptosis in Thyroid Cells J. Biol. Chem., June 9, 2000; 275(24): 18266 - 18270. [Abstract] [Full Text] [PDF]
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