title: TRAIL and DcR1 expressions are differentially regulated in the pancreatic islets of STZ- versus CY-applied NOD mice.
abstract: TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D) development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD) mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1) expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development.
authors.affiliation: Section of Islet Cell and Regenerative Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Ercument
authors.initials: E
authors.lastname: Dirice
authors.forename: Sevim
authors.initials: S
authors.lastname: Kahraman
authors.forename: Gulsum Ozlem
authors.initials: GO
authors.lastname: Elpek
authors.forename: Cigdem
authors.initials: C
authors.lastname: Aydin
authors.forename: Mustafa Kemal
authors.initials: MK
authors.lastname: Balci
authors.forename: Abdulkadir
authors.initials: A
authors.lastname: Omer
authors.forename: Salih
authors.initials: S
authors.lastname: Sanlioglu
authors.forename: Ahter Dilsad
authors.initials: AD
authors.lastname: Sanlioglu
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D053320:Receptors, Tumor Necrosis Factor, Member 10c / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D013311:Streptozocin; D003520:Cyclophosphamide