@article {7730, title = {TRAIL modulates the immune system and protects against the development of diabetes.}, journal = {J Immunol Res}, volume = {2015}, year = {2015}, month = {2015}, pages = {680749}, abstract = {

TRAIL or tumor necrosis factor (TNF) related apoptosis-inducing ligand is a member of the TNF superfamily of proteins, whose best characterized function is the induction of apoptosis in tumor, infected, or transformed cells through activation of specific receptors. In nontransformed cells, however, the actions of TRAIL are less well characterized. Recent studies suggest that TRAIL may be implicated in the development and progression of diabetes. Here we review TRAIL biological actions, its effects on the immune system, and how and to what extent it has been shown to protect against diabetes.

}, keywords = {Animals, Diabetes Mellitus, Humans, Immune System, Receptors, TNF-Related Apoptosis-Inducing Ligand, Signal Transduction}, issn = {2314-7156}, doi = {10.1155/2015/680749}, author = {Bossi, Fleur and Bernardi, Stella and Zauli, Giorgio and Secchiero, Paola and Fabris, Bruno} } @article {1911, title = {TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation.}, journal = {Clin Sci (Lond)}, volume = {123}, year = {2012}, month = {2012 Nov}, pages = {547-55}, abstract = {

TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has recently been shown to ameliorate the natural history of DM (diabetes mellitus). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27 male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or HFD+TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory cytokines, together with adipose tissue gene expression and apoptosis, were measured. TRAIL treatment reduced significantly the increased adiposity associated with an HFD. Moreover, it reduced significantly hyperglycaemia and hyperinsulinaemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis. These findings shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and T2DM (Type 2 DM).

}, keywords = {Adiposity, Animals, Apoptosis, Calorimetry, Cytokines, Dietary Fats, Energy Intake, Glucose Tolerance Test, Hyperglycemia, Hyperinsulinism, Inflammation, Inflammation Mediators, Male, Mice, Mice, Inbred C57BL, Oxidation-Reduction, Palmitic Acid, Real-Time Polymerase Chain Reaction, TNF-Related Apoptosis-Inducing Ligand}, issn = {1470-8736}, doi = {10.1042/CS20120176}, author = {Bernardi, Stella and Zauli, Giorgio and Tikellis, Christos and Candido, Riccardo and Fabris, Bruno and Secchiero, Paola and Cooper, Mark E and Thomas, Merlin C} } @article {1917, title = {TRAIL as biomarker and potential therapeutic tool for cardiovascular diseases.}, journal = {Curr Drug Targets}, volume = {13}, year = {2012}, month = {2012 Aug}, pages = {1215-21}, abstract = {

This review focuses on TNF-related apoptosis-inducing ligand (TRAIL), also called Apo2 ligand, a protein belonging to the TNF superfamily. TRAIL can be found either in its transmembrane or circulating form, and its mostly studied peripheral effect is the induction of cellular apoptosis. Here, we discuss the evidences supporting the use of TRAIL as biomarker of cardiovascular diseases as well as the evidences showing the potential beneficial therapeutic effects of TRAIL on cardiovascular diseases and diabetes.

}, keywords = {Biological Markers, Cardiovascular Diseases, Humans, Prognosis, TNF-Related Apoptosis-Inducing Ligand}, issn = {1873-5592}, author = {Bernardi, Stella and Milani, Daniela and Fabris, Bruno and Secchiero, Paola and Zauli, Giorgio} } @article {1709, title = {TRAIL shows potential cardioprotective activity.}, journal = {Invest New Drugs}, volume = {30}, year = {2012}, month = {2012 Jun}, pages = {1257-60}, abstract = {

Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated that TRAIL (administrated as either recombinant soluble TRAIL or as AAV-TRAIL expression viral vector) reduced the development of cardiomyopathy in the ApoE(-/-) diabetic mouse model. These data suggest, for the first time, that therapeutically administration of TRAIL might have a cardioprotective effect.

}, keywords = {Animals, Apolipoproteins E, Apoptosis, Cardiotonic Agents, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetic Cardiomyopathies, Fibrosis, Male, Mice, Mice, Knockout, Recombinant Proteins, TNF-Related Apoptosis-Inducing Ligand}, issn = {1573-0646}, doi = {10.1007/s10637-010-9627-8}, author = {Toffoli, Barbara and Bernardi, Stella and Candido, Riccardo and Zacchigna, Serena and Fabris, Bruno and Secchiero, Paola} } @article {1718, title = {Treatment with recombinant tumor necrosis factor-related apoptosis-inducing ligand alleviates the severity of streptozotocin-induced diabetes.}, journal = {Diabetes}, volume = {59}, year = {2010}, month = {2010 May}, pages = {1261-5}, abstract = {

OBJECTIVE: To evaluate the potential therapeutic effect of recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) treatment in a model of type 1 diabetes.

RESEARCH DESIGN AND METHODS: Recombinant TRAIL was added in vitro to primary human and mouse peripheral blood mononuclear cells (PBMCs) and isolated human islets to evaluate the expression of the immunoregulatory gene SOCS1. Diabetes was induced by five consecutive daily injections of low-concentration (50 mg/kg) streptozotocin (STZ) in C57 black mice (n = 24). A group of these mice (n = 12) was co-injected with recombinant TRAIL (20 microg/day) for 5 days, and the diabetic status (glycemia and body weight) was followed over time. After 6 weeks, circulating levels of insulin, TNF-alpha, and osteoprotegerin (OPG) were measured, and animals were killed to perform the histological analysis of the pancreas.

RESULTS: The in vitro exposure of both PBMCs and human islets to recombinant TRAIL significantly upregulated the expression of SOCS1. With respect to STZ-treated animals, mice co-injected with STZ+TRAIL were characterized by 1) lower levels of hyperglycemia, 2) higher levels of body weight and insulinemia, 3) a partial preservation of pancreatic islets with normal morphology, and 4) a lower expression of both systemic (TNF-alpha and OPG) and pancreatic (vascular cell adhesion molecule [VCAM]-1) inflammatory markers.

CONCLUSIONS: Overall, these data demonstrate that the administration of recombinant TRAIL ameliorates the severity of STZ-induced type 1 diabetes, and this effect was accompanied by the upregulation of SOCS1 expression.

}, keywords = {Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Gene Expression, Humans, Islets of Langerhans, Leukocytes, Mononuclear, Mice, Recombinant Proteins, Suppressor of Cytokine Signaling Proteins, TNF-Related Apoptosis-Inducing Ligand}, issn = {1939-327X}, doi = {10.2337/db09-1771}, author = {Zauli, Giorgio and Toffoli, Barbara and di Iasio, Maria Grazia and Celeghini, Claudio and Fabris, Bruno and Secchiero, Paola} }