title: 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.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07058, Antalya, Turkey; Center for Gene and Cell Therapy, Akdeniz University, 07058 Antalya, Turkey.
authors.forename: Irem
authors.initials: I
authors.lastname: Kanatli
authors.affiliation: Department of Pathology, Faculty of Medicine, Akdeniz University, 07058 Antalya, Turkey.
authors.forename: Bahar
authors.initials: B
authors.lastname: Akkaya
authors.affiliation: Department of Neurology, Faculty of Medicine, Akdeniz University, 07058 Antalya, Turkey.
authors.forename: Hilmi
authors.initials: H
authors.lastname: Uysal
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07058, Antalya, Turkey; Center for Gene and Cell Therapy, Akdeniz University, 07058 Antalya, Turkey.
authors.forename: Sevim
authors.initials: S
authors.lastname: Kahraman
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07058, Antalya, Turkey; Center for Gene and Cell Therapy, Akdeniz University, 07058 Antalya, Turkey. Electronic address: ahter@icloud.com.
authors.forename: Ahter Dilsad
authors.initials: AD
authors.lastname: Sanlioglu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D002452:Cell Count; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013934:Thymectomy; D060168:Thymocytes / Q000502:physiology; D013945:Thymoma / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology; D013952:Thymus Hyperplasia / Q000378:metabolism* / Q000473:pathology; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human
keywords: Medical thymectomy; Myasthenia Gravis; TRAIL; Thymic hyperplasia; Thymoma