Limits...
TRAIL modulates the immune system and protects against the development of diabetes.

Bossi F, Bernardi S, Zauli G, Secchiero P, Fabris B - J Immunol Res (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical, Surgical, and Health Sciences, University of Trieste, Cattinara University Hospital, Strada di Fiume 447, 34100 Trieste, Italy.

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.

Show MeSH

Related in: MedlinePlus

TRAIL reduces CD3 infiltration. CD3 count and representative histological sections of pancreas islets from standard diet (SD), high-fat diet (HF), or high-fat diet fed mice treated with TRAIL (HF + TRAIL) (magnification 20x). The sections were stained with polyclonal antibody against CD3 (3,3′-diaminobenzidine-DAB) and counterstained with hematoxylin. Pancreatic CD3 infiltration was estimated by determining the total number of cells positive for CD3 per islet. Data are mean ± SEM *P < 0.01 versus SD; #P < 0.01 versus HF.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4352427&req=5

fig4: TRAIL reduces CD3 infiltration. CD3 count and representative histological sections of pancreas islets from standard diet (SD), high-fat diet (HF), or high-fat diet fed mice treated with TRAIL (HF + TRAIL) (magnification 20x). The sections were stained with polyclonal antibody against CD3 (3,3′-diaminobenzidine-DAB) and counterstained with hematoxylin. Pancreatic CD3 infiltration was estimated by determining the total number of cells positive for CD3 per islet. Data are mean ± SEM *P < 0.01 versus SD; #P < 0.01 versus HF.

Mentions: Animal studies suggest that TRAIL might protect against T2DM too. Di Bartolo and colleagues found that TRAIL deficiency promoted diabetes development in ApoE/TRAIL-knockout mice put on a high-fat diet [53], which is commonly used to induce obesity and insulin resistance in rodents [88, 101, 102]. In particular, ApoE/TRAIL-knockout mice displayed significantly higher glucose levels and lower insulin levels than ApoE-knockout mice. Consequently, this study showed that TRAIL deficiency significantly worsened glucose tolerance, and this was associated with β-cell function impairment, β-cell density reduction, and an increase in islet macrophage infiltration. Consistent with this we have documented the ability of TRAIL to significantly reverse the metabolic abnormalities due to an oversupply of lipids and thus to slow down the natural progression of T2DM [101]. In particular, we studied 27 male C57Bl6J mice randomly allocated to standard diet (SD), high-fat diet (HF), and high-fat diet + TRAIL (HF + TRAIL) for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection at a dose of 10 μg per mouse. At the end of the study we found that TRAIL treatment reduced significantly the hyperglycemia and the hyperinsulinemia displayed by the high-fat diet fed mice during an IPGTT. Moreover, TRAIL treatment significantly reduced the β-cell hypertrophy and the β-cell loss, as it reduced β-cell mass and increased β-cell density (Figure 3). This was associated with a decrease in protein nitrosylation (data not shown), as well as with a significant reduction in CD3 infiltration (Figure 4) in the islets of TRAIL treated high-fat diet fed mice. This is of relevance since lymphocyte-driven autoimmune assault is one of the mechanisms accounting for β-cell destruction in T2DM [96]. Interestingly, we have also shown that OPG, which is TRAIL decoy receptor, has opposite actions to those of TRAIL, as it seems to promote glucose intolerance [88, 103].


TRAIL modulates the immune system and protects against the development of diabetes.

Bossi F, Bernardi S, Zauli G, Secchiero P, Fabris B - J Immunol Res (2015)

TRAIL reduces CD3 infiltration. CD3 count and representative histological sections of pancreas islets from standard diet (SD), high-fat diet (HF), or high-fat diet fed mice treated with TRAIL (HF + TRAIL) (magnification 20x). The sections were stained with polyclonal antibody against CD3 (3,3′-diaminobenzidine-DAB) and counterstained with hematoxylin. Pancreatic CD3 infiltration was estimated by determining the total number of cells positive for CD3 per islet. Data are mean ± SEM *P < 0.01 versus SD; #P < 0.01 versus HF.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352427&req=5

fig4: TRAIL reduces CD3 infiltration. CD3 count and representative histological sections of pancreas islets from standard diet (SD), high-fat diet (HF), or high-fat diet fed mice treated with TRAIL (HF + TRAIL) (magnification 20x). The sections were stained with polyclonal antibody against CD3 (3,3′-diaminobenzidine-DAB) and counterstained with hematoxylin. Pancreatic CD3 infiltration was estimated by determining the total number of cells positive for CD3 per islet. Data are mean ± SEM *P < 0.01 versus SD; #P < 0.01 versus HF.
Mentions: Animal studies suggest that TRAIL might protect against T2DM too. Di Bartolo and colleagues found that TRAIL deficiency promoted diabetes development in ApoE/TRAIL-knockout mice put on a high-fat diet [53], which is commonly used to induce obesity and insulin resistance in rodents [88, 101, 102]. In particular, ApoE/TRAIL-knockout mice displayed significantly higher glucose levels and lower insulin levels than ApoE-knockout mice. Consequently, this study showed that TRAIL deficiency significantly worsened glucose tolerance, and this was associated with β-cell function impairment, β-cell density reduction, and an increase in islet macrophage infiltration. Consistent with this we have documented the ability of TRAIL to significantly reverse the metabolic abnormalities due to an oversupply of lipids and thus to slow down the natural progression of T2DM [101]. In particular, we studied 27 male C57Bl6J mice randomly allocated to standard diet (SD), high-fat diet (HF), and high-fat diet + TRAIL (HF + TRAIL) for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection at a dose of 10 μg per mouse. At the end of the study we found that TRAIL treatment reduced significantly the hyperglycemia and the hyperinsulinemia displayed by the high-fat diet fed mice during an IPGTT. Moreover, TRAIL treatment significantly reduced the β-cell hypertrophy and the β-cell loss, as it reduced β-cell mass and increased β-cell density (Figure 3). This was associated with a decrease in protein nitrosylation (data not shown), as well as with a significant reduction in CD3 infiltration (Figure 4) in the islets of TRAIL treated high-fat diet fed mice. This is of relevance since lymphocyte-driven autoimmune assault is one of the mechanisms accounting for β-cell destruction in T2DM [96]. Interestingly, we have also shown that OPG, which is TRAIL decoy receptor, has opposite actions to those of TRAIL, as it seems to promote glucose intolerance [88, 103].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical, Surgical, and Health Sciences, University of Trieste, Cattinara University Hospital, Strada di Fiume 447, 34100 Trieste, Italy.

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.

Show MeSH
Related in: MedlinePlus