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Science 14 February 1997:
Vol. 275. no. 5302, pp. 960 - 963
DOI:

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Reports

Potential Involvement of Fas and Its Ligand in the Pathogenesis of Hashimoto's Thyroiditis

Carla Giordano, * Giorgio Stassi, * Ruggero De Maria, * Matilde Todaro, Pierina Richiusa, Giuliana Papoff, Giovina Ruberti, Marcello Bagnasco, Roberto Testi, dagger Aldo Galluzzo

The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1beta (IL-1beta ), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta -induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism.

C. Giordano, G. Stassi, M. Todaro, P. Richiusa, A. Galluzzo, Laboratory of Immunology, Endocrinology Section, Institute of Clinica Medica, University of Palermo, Palermo, Italy.
R. De Maria and R. Testi, Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata," Rome, Italy.
G. Papoff and G. Ruberti, Department of Immunobiology, Institute of Cell Biology, CNR, Rome, Italy.
M. Bagnasco, Allergology and Clinical Immunology, University of Genova, Genoa, Italy.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: tesrob{at}flashnet.it

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   Abstract »    Full Text »
Functional Fas Expression in Human Thymic Epithelial Cells.
N. Moulian, C. Renvoize, C. Desodt, A. Serraf, and S. Berrih-Aknin (1999)
Blood 93, 2660-2670
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1{alpha},25-Dihydroxyvitamin D3 Up-Regulates Bcl-2 Expression and Protects Normal Human Thyrocytes from Programmed Cell Death.
S. H. Wang, R. J. Koenig, T. J. Giordano, A. Myc, N. W. Thompson, and J. R. Baker Jr. (1999)
Endocrinology 140, 1649-1656
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Dissecting Fas signaling with an altered-specificity death-domain mutant: Requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation.
H. Y. Chang, X. Yang, and D. Baltimore (1999)
PNAS 96, 1252-1256
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Apoptotic Role of Fas/Fas Ligand System in the Regulation of Erythropoiesis.
R. De Maria, U. Testa, L. Luchetti, A. Zeuner, G. Stassi, E. Pelosi, R. Riccioni, N. Felli, P. Samoggia, and C. Peschle (1999)
Blood 93, 796-803
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Withdrawal of Survival Factors Results in Activation of the JNK Pathway in Neuronal Cells Leading to Fas Ligand Induction and Cell Death.
H. Le-Niculescu, E. Bonfoco, Y. Kasuya, F.-X. Claret, D. R. Green, and M. Karin (1999)
Mol. Cell. Biol. 19, 751-763
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Fas/Fas Ligand-Driven T Cell Apoptosis as a Consequence of Ineffective Thyroid Immunoprivilege in Hashimoto's Thyroiditis.
G. Stassi, M. Todaro, F. Bucchieri, A. Stoppacciaro, F. Farina, G. Zummo, R. Testi, and R. D. Maria (1999)
J. Immunol. 162, 263-267
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Gene Therapy of Experimental Autoimmune Thyroiditis by In Vivo Administration of Plasmid DNA Coding for Fas Ligand.
F. Batteux, L. Tourneur, H. Trebeden, J. Charreire, and G. Chiocchia (1999)
J. Immunol. 162, 603-608
   Abstract »    Full Text »    PDF »
Role of T-helper type 2 cytokines in down-modulation of Fas mRNA and receptor on the surface of activated CD4+ T cells: molecular basis for the persistence of the allergic immune response.
F. Spinozzi, E. Agea, M. Fizzotti, G. Bassotti, A. Russano, S. Droetto, O. Bistoni, F. Grignani, and A. Bertotto (1998)
FASEB J 12, 1747-1753
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T Cell Apoptosis in Human Heart Allografts : Association with Lack of Co-Stimulation?.
E. Van Hoffen, D. F. Van Wichen, J. C. Leemans, R. A.J.F. Broekhuizen, A. H. Bruggink, M. De Boer, N. De Jonge, H. Kirkels, P. J. Slootweg, F. H.J. Gmelig-Meyling, et al. (1998)
Am. J. Pathol. 153, 1813-1824
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B7.1 Costimulatory Molecule Is Expressed on Thyroid Follicular Cells in Hashimoto's Thyroiditis, But Not in Graves' Disease.
M. Battifora, G. Pesce, F. Paolieri, N. Fiorino, C. Giordano, A. M. Riccio, G. Torre, D. Olive, and M. Bagnasco (1998)
J. Clin. Endocrinol. Metab. 83, 4130-4139
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Somatic Fas Mutations in Non-Hodgkin's Lymphoma: Association With Extranodal Disease and Autoimmunity.
K. Gronbak, P. t. Straten, E. Ralfkiaer, V. Ahrenkiel, M. K. Andersen, N. E. Hansen, J. Zeuthen, K. Hou-Jensen, and P. Guldberg (1998)
Blood 92, 3018-3024
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Case 33-1998- A 29-Year-Old Woman with Necrotizing Lymphadenitis, the Nephrotic Syndrome, and Acute Renal Failure.
M. P. Madaio and R. T. McCluskey (1998)
N. Engl. J. Med. 339, 1308-1317
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Inhibition of Toxic Epidermal Necrolysis by Blockade of CD95 with Human Intravenous Immunoglobulin.
I. Viard, P. Wehrli, R. Bullani, P. Schneider, N. Holler, D. Salomon, T. Hunziker, J. Saurat, J. Tschopp, and L. E. French (1998)
Science 282, 490-493
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Expression of Fas (CD95) and FasL (CD95L) in Human Airway Epithelium.
K. J. Hamann, D. R. Dorscheid, F. D. Ko, A. E. Conforti, A. I. Sperling, K. F. Rabe, and S. R. White (1998)
Am. J. Respir. Cell Mol. Biol. 19, 537-542
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Therapeutic Preparations of Normal Polyspecific IgG (IVIg) Induce Apoptosis in Human Lymphocytes and Monocytes: A Novel Mechanism of Action of IVIg Involving the Fas Apoptotic Pathway.
N. K. A. Prasad, G. Papoff, A. Zeuner, E. Bonnin, M. D. Kazatchkine, G. Ruberti, and S. V. Kaveri (1998)
J. Immunol. 161, 3781-3790
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Role of Apoptosis of Thyrocytes in a Rat Model of Goiter. A Possible Involvement of Fas System.
M. Tamura, H. Kimura, T. Koji, T. Tominaga, K. Ashizawa, T. Kiriyama, N. Yokoyama, T. Yoshimura, K. Eguchi, P. K. Nakane, et al. (1998)
Endocrinology 139, 3646-3653
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Cyclosporin A-Sensitive Transcription Factor Egr-3 Regulates Fas Ligand Expression.
P. R. Mittelstadt and J. D. Ashwell (1998)
Mol. Cell. Biol. 18, 3744-3751
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Apoptosis: Programmed Cell Death.
N.-K. Kuan and E. Passaro Jr (1998)
Arch Surg 133, 773-775
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Fas/Fas Ligand Up-Regulation and BCL-2 Down-Regulation May Be Significant in the Pathogenesis of Hashimoto's Thyroiditis.
N. Mitsiades, V. Poulaki, V. Kotoula, G. Mastorakos, S. Tseleni-Balafouta, D. A. Koutras, and M. Tsokos (1998)
J. Clin. Endocrinol. Metab. 83, 2199-2203
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Differential Sensitivity of CD4+ and CD8+ T Lymphocytes to the Killing Efficacy of Fas (Apo-1/CD95) Ligand+ Tumor Cells in B Chronic Lymphocytic Leukemia.
I. Tinhofer, I. Marschitz, M. Kos, T. Henn, A. Egle, A. Villunger, and R. Greil (1998)
Blood 91, 4273-4281
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Technical Note: Aberrant Detection of Cell Surface Fas Ligand with Anti-Peptide Antibodies.
D. Smith, S. Sieg, and D. Kaplan (1998)
J. Immunol. 160, 4159-4160
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Ultraviolet Light-Induced Immune Tolerance Is Mediated via the Fas/Fas-Ligand System.
A. Schwarz, S. Grabbe, K. Grosse-Heitmeyer, B. Roters, H. Riemann, T. A. Luger, G. Trinchieri, and T. Schwarz (1998)
J. Immunol. 160, 4262-4270
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Elevation of the Serum Fas Ligand in Patients With Hemophagocytic Syndrome and Diamond-Blackfan Anemia.
D. Hasegawa, S. Kojima, E. Tatsumi, A. Hayakawa, Y. Kosaka, H. Nakamura, M. Sako, Y. Osugi, S. Nagata, and K. Sano (1998)
Blood 91, 2793-2799
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Fas Ligand Is Present in Human Erythroid Colony-Forming Cells and Interacts With Fas Induced by Interferon gamma  to Produce Erythroid Cell Apoptosis.
C.-H. Dai, J. O. Price, T. Brunner, and S. B. Krantz (1998)
Blood 91, 1235-1242
   Abstract »    Full Text »    PDF »


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