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

Abstract

Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (~10%) or hyperplastic thymus (~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.

• Authors: Irem Kanatli, Bahar Akkaya, Hilmi Uysal, Sevim Kahraman, Ahter Dilsad Sanlioglu
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 27 Issue 2 Pg. 128-135 (Feb 2017) ISSN: 1873-2364 [Electronic] England
• PMID: 28012741 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10A protein, human
• TNFRSF10B protein, human
• TNFSF10 protein, human

Topics

• Adult
• Aged
• Apoptosis (physiology)
• Cell Count
• Female
• Humans
• Male
• Middle Aged
• Myasthenia Gravis (metabolism, pathology)
• NF-kappa B (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Thymectomy
• Thymocytes (physiology)
• Thymoma (metabolism, pathology)
• Thymus Gland (metabolism, pathology)
• Thymus Hyperplasia (metabolism, pathology)
• Thymus Neoplasms (metabolism, pathology)