Analysis of TNF-related apoptosis-inducing ligand and receptors and implications in thymus biology and myasthenia gravis

Kanatli I., AKKAYA B., UYSAL H., Kahraman S., ŞANLIOĞLU A. D.

NEUROMUSCULAR DISORDERS, cilt.27, sa.2, ss.128-135, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 2
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.nmd.2016.10.012
  • Dergi Adı: NEUROMUSCULAR DISORDERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.128-135
  • Anahtar Kelimeler: Myasthenia Gravis, Thymoma, Thymic hyperplasia, TRAIL, Medical thymectomy, NF-KAPPA-B, PROSTATE CARCINOMA-CELLS, LUNG-CANCER CELLS, ADENOVIRUS DELIVERY, THYMOCYTE APOPTOSIS, NEGATIVE SELECTION, IN-VITRO, TRAIL, DEATH, EXPRESSION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (similar to 10%) or hyperplastic thymus (similar to 65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma-or thymic hyperplasia-associated Myasthenia Gravis is also discussed. (C) 2016 Elsevier B.V. All rights reserved.