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Interferon-γ inhibits integrin-mediated extracellular signal-regulated kinase activation stimulated by fibronectin binding in thyroid cells

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Abstract

Hashimoto’s thyroiditis (HT) is an autoimmune disorder characterized by the presence of specific antibodies and by a lymphocytic infiltration of the thyroid secreting inflammatory cytokines. Macrophages, lymphocytes, and cytokines play a pivotal role in both development and progression of Th1-mediated autoimmune diseases, and a direct role in the destruction of thyroid follicles and follicular cell function in autoimmune thyroiditis. Integrins are integral membrane receptors involved in cell-extra-cellular matrix (ECM) interaction with both structural and signaling functions. The integrin-ECM interaction is necessary for the correct function and survival of thyroid follicular cells. The purpose of this study was to determine the effect of cytokine stimulation on integrin expression and signaling in the thyroid cell. Primary cultures from normal thyroids were treated with interferon-γ (IFN-γ), INF-α, tumor necrosis factor-α, interlukin 1a or these cytokines all together. Integrin expression, cell adhesion to fibronectin (FN) and FN-stimulated extracellular signal-regulated kinase (ERK) phosphorylation were determined after cytokine treatment. IFN-γ and IFN-α were the most effective, reducing the expression of the integrin αvβ3 and slightly increasing the α3β1. Cell treatment with IFN-γ strongly impaired cell adhesion to FN. At the same time, the treatment with IFN-γ dramatically inhibited the stimulation of ERK phosphorylation induced by cell adhesion to FN. In conclusion, IFN-γ inhibits the expression of the integrin αvβ3, reducing the cell adhesion to FN and the following intracellular signaling in thyroid cells in culture. These results suggest that integrins may be a target of the infiltrating lymphocytes and have a role in the pathogenesis of autoimmune thyroiditis.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University, Naples, Italy

    E. Russo, M. Salzano & L. Postiglione

  2. Department of Medicine and Surgery, University of Salerno, Via Allende, 84081, Baronissi, Salerno, Italy

    A. Guerra & M. Vitale

  3. Department of Clinical and Molecular Endocrinology and Oncology, “Federico II” University, Naples, Italy

    V. Marotta

Authors
  1. E. Russo
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  2. M. Salzano
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  3. L. Postiglione
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  4. A. Guerra
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  5. V. Marotta
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  6. M. Vitale
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Correspondence to M. Vitale.

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Russo, E., Salzano, M., Postiglione, L. et al. Interferon-γ inhibits integrin-mediated extracellular signal-regulated kinase activation stimulated by fibronectin binding in thyroid cells. J Endocrinol Invest 36, 375–378 (2013). https://doi.org/10.3275/8649

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  • DOI: https://doi.org/10.3275/8649

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