Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death

Zaitseva, Irina I.; Hultcrantz, Monica; Sharoyko, Vladimir V.; Flodström‐Tullberg, Malin; Зайцев, С. В.; Berggren, Per Olof

doi:10.1007/s00018-009-0151-y

Cited by 13 publications

(12 citation statements)

References 57 publications

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“…In addition, increased expressions of SOCS5 and SOCS6 were detected in ovary and lung cancer tissues. Considering that increased SOCS1 and SOCS3 expressions were associated with reduced activity of apoptotic pathways in some cancer tissues [30,31], it is possible that SOCS5 and SOCS6 may have the function in the increased levels in those cancer tissues. In order to confirm the results from our study, normal and cancer tissue samples from other populations should be evaluated in future studies.…”

Section: Discussionmentioning

confidence: 98%

SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues

Yoon

Kim

et al. 2011

Tumor Biol.

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In the present study, we investigated mRNA expression patterns of both SOCS5 and SOCS6 in various normal and cancer tissues using a commercially available Cancer Profiling Array. We found that SOCS5 and SOCS6 had similar expression patterns in most cancer and healthy individuals, suggesting that these two genes are transcriptionally co-regulated. Tissue-specific up- or down-regulation of SOCS5 and SOCS6 was observed in several cancer tissues. Most importantly, thyroid gland cancer tissues exhibited large reductions of both SOCS5 and SOCS6 expressions. In addition, mRNA and protein levels of SOCS6 were down-regulated in liver cancer tissues. The results from our study may contribute to understanding SOCS5 and SOCS6 expression regulation in various cancer tissues, and show that these two factors may be used for diagnosing cancer.

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Section: Discussionmentioning

confidence: 98%

SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues

Yoon

Kim

et al. 2011

Tumor Biol.

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“…Interestingly, we have also shown that recombinant TRAIL might increase SOCS1 expression also at the pancreatic level. This is particularly remarkable, since increasing SOCS1 expression in β-cells has been shown to inhibit TNF-induced Fas expression in vitro and prevent the progression to diabetes in NOD mice (21–23), and the overexpression of SOCS1 in islet grafts may inhibit or block the apoptotic pathway and prolong graft survival (22). …”

Section: Discussionmentioning

confidence: 99%

Treatment With Recombinant Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Alleviates the Severity of Streptozotocin-Induced Diabetes

et al. 2010

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OBJECTIVETo 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 METHODSRecombinant 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 μg/day) for 5 days, and the diabetic status (glycemia and body weight) was followed over time. After 6 weeks, circulating levels of insulin, TNF-α, and osteoprotegerin (OPG) were measured, and animals were killed to perform the histological analysis of the pancreas.RESULTSThe 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-α and OPG) and pancreatic (vascular cell adhesion molecule [VCAM]-1) inflammatory markers.CONCLUSIONSOverall, 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.

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“…Genetic and pharmacological inhibition of ATF6 significantly suppresses NF-κB activation, which can transcriptionally regulate many other inflammatory genes 34. Activation of either JNKs or NF-κB pathways in pancreatic β-cells has been reported to cause increased expression of proinflammatory molecules, such as IL-8, IL-6, monocyte chemotactic protein-1, and tumor necrosis factor-α,35 that have a detrimental effect on cell survival and function 36–38. Local chemokine and cytokine release can also contribute to the inflammatory milieu, attracting host macrophages to the pancreatic β-cells, which further propagate local inflammation 39,40.…”

Section: The Link Between Stress and Inflammation In Pancreatic β-Cellsmentioning

confidence: 99%

Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes

Montané

Cadavez

Novials

2014

DMSO

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Type 2 diabetes (T2D) is a complex metabolic disorder characterized by hyperglycemia in the context of insulin resistance, which precedes insulin deficiency as a result of β-cell failure. Accumulating evidence indicates that β-cell loss in T2D results as a response to the combination of oxidative stress and endoplasmic reticulum (ER) stress. Failure of the ER’s adaptive capacity and further activation of the unfolded protein response may trigger macroautophagy (hereafter referred as autophagy) as a process of self-protection and inflammation. Many studies have shown that inflammation plays a very important role in the pathogenesis of T2D. Inflammatory mechanisms and cytokine production activated by stress via the inflammasome may further alter the normal structure of β-cells by inducing pancreatic islet cell apoptosis. Thus, the combination of oxidative and ER stress, together with autophagy insufficiency and inflammation, may contribute to β-cell death or dysfunction in T2D. Therapeutic approaches aimed at ameliorating stress and inflammation may therefore prove to be promising targets for the development of new diabetes treatment methods. Here, we discuss different mechanisms involved in stress and inflammation, and the role of antioxidants, endogenous and chemical chaperones, and autophagic pathways, which may shift the tendency from ER stress and apoptosis toward cell survival. Strategies targeting cell survival can be essential for relieving ER stress and reestablishing homeostasis, which may diminish inflammation and prevent pancreatic β-cell death associated with T2D.

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Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death

Cited by 13 publications

References 57 publications

SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues

SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues

Treatment With Recombinant Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Alleviates the Severity of Streptozotocin-Induced Diabetes

Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes

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