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Research ArticleMinireviews

Pharmacological Modulation of Caspase-8 in Thymus-Related Medical Conditions

Nicola Pozzesi, Alessandra Fierabracci, Trinh Thy Thuy, Maria Paola Martelli, Anna Marina Liberati, Emira Ayroldi, Carlo Riccardi and Domenico V. Delfino
Journal of Pharmacology and Experimental Therapeutics October 2014, 351 (1) 18-24; DOI: https://doi.org/10.1124/jpet.114.216572
Nicola Pozzesi
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Alessandra Fierabracci
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Trinh Thy Thuy
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Maria Paola Martelli
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Anna Marina Liberati
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Emira Ayroldi
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Carlo Riccardi
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Domenico V. Delfino
Foligno Nurse School, Department of Medicine (N.P.), Section of Hematology (M.P.M.), Section of Pharmacology (E.A., C.R., D.V.D.), Department of Medicine, Section of Onco-Hematology, Hospital S. Maria, Terni, Department of Surgery (A.M.L.), University of Perugia, Perugia, Italy; Autoimmunity Laboratory, Immunology and Pharmacotherapy Area, Bambin Gesù Children’s Hospital IRCCS, Rome, Italy (A.F.); and Institute of Chemistry, Vietnam Academy of Science and Technology, Cau Giay, Hanoi, Vietnam (T.T.T.)
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Abstract

The thymus is a lymphoid organ that governs the development of a diverse T-cell repertoire capable of defending against nonself-antigens and avoiding autoimmunity. However, the thymus can also succumb to different diseases. Hypertrophic diseases, such as thymomas, are typically associated with impairment of negative selection, which leads to autoimmune disease, or disruption of positive selection, which results in immunodeficiency. Hypotrophic diseases of the thymus can manifest during acute infections, cancer, allogeneic bone marrow transplantation, or with aging. This condition leads to decreased immune function and can be treated by either replacing lost thymic tissue or by preventing thymic tissue death. Studies have demonstrated the critical role of caspase-8 in regulating apoptosis in the thymus. In this review, we discuss how pharmacological activation and inhibition of caspase-8 can be used to treat hypertrophic and hypotrophic diseases of the thymus, respectively, to improve its function.

Footnotes

    • Received May 16, 2014.
    • Accepted July 23, 2014.
  • This work was supported in part by the Italian Ministero degli Esteri, AIRC, and Vietnamese MOST.

  • dx.doi.org/10.1124/jpet.114.216572.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 351 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 351, Issue 1
1 Oct 2014
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Research ArticleMinireviews

Caspase-8 and Thymic Diseases

Nicola Pozzesi, Alessandra Fierabracci, Trinh Thy Thuy, Maria Paola Martelli, Anna Marina Liberati, Emira Ayroldi, Carlo Riccardi and Domenico V. Delfino
Journal of Pharmacology and Experimental Therapeutics October 1, 2014, 351 (1) 18-24; DOI: https://doi.org/10.1124/jpet.114.216572

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Research ArticleMinireviews

Caspase-8 and Thymic Diseases

Nicola Pozzesi, Alessandra Fierabracci, Trinh Thy Thuy, Maria Paola Martelli, Anna Marina Liberati, Emira Ayroldi, Carlo Riccardi and Domenico V. Delfino
Journal of Pharmacology and Experimental Therapeutics October 1, 2014, 351 (1) 18-24; DOI: https://doi.org/10.1124/jpet.114.216572
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