Identification of Interleukin 1-induced Apoptosis in Rat Islets Usingin situSpecific Labelling of Fragmented DNA

Dunger, A; Augstein, Petra; Schmidt, S.; Fischer, Uwe

doi:10.1006/jaut.1996.0042

Cited by 46 publications

(25 citation statements)

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“…However, high glucose potentiation of the apoptotic effects of cytokines was greater than the potentiation of the apoptotic effects of STZ in these conditions. Both STZ (Turk et al 1993) and cytokines (Kaneto et al 1995, Dunger et al 1996 have been shown to induce apoptosis in -cells and it is known that glucose concentration modifies mouse islet loss after STZ treatment (Eizirik et al 1988), but the mechanisms involved are not well understood (Suarez-Pinzon et al 1994). Our results suggest that mechanisms involved in cytokine-induced apoptosis could be more amplified by high glucose-induced hyperfunctional status of islet cells than the mechanisms implicated in STZ-mediated apoptotic effects.…”

Section: Discussionmentioning

confidence: 38%

“…Although the mechanism of this destruction is not completely understood, -cell apoptosis is known to participate in this process (O'Brien et al 1997, Kurrer et al 1997, Augstein et al 1998. Interleukin (IL)-1 alone or in combination with other pro-inflammatory cytokines inhibits the glucoseinduced insulin secretion and plays an important role in -cell death by inducing toxic nitric oxide (NO) in the islet (Kaneto et al 1995, Dunger et al 1996, MandrupPoulsen 1996. Streptozotocin (STZ) has been used widely to produce animal models of diabetes.…”

Section: Introductionmentioning

confidence: 99%

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High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes

Mellado-Gil¹,

Diosdado²

2004

Journal of Endocrinology

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Pancreatic -cell apoptosis is known to participate in the -cell destruction process that occurs in diabetes. A better understanding of how it takes place is essential for future development of therapeutic strategies aimed at preventing -cell loss and diabetes. In this study we determine the possible role that high glucose concentration might play as an enhancer of cytokine-and streptozotocin (STZ)-mediated rat islet cell apoptosis in vitro and its relationship with potential changes in the expression of pro-and anti-apoptotic proteins. Rat islets treated with a cytokine combination (interleukin (IL)-1 , tumor necrosis factor (TNF)-and interferon (IFN)-) displayed a significant increase in islet cell apoptosis when the islets were incubated in 24·4 mM glucose compared with untreated islets at the same glucose concentration (13·07 1·78% vs 6·09 0·78%; P<0·01) or islets incubated in 5·5 mM glucose concentration and cytokines (13·07 1·78% vs 8·04 1·56%; P<0·05). IL-1 alone did not induce a significant increase in the apoptotic rates in islet cells cultured at normal or high glucose concentrations. STZ significantly increased islet cell apoptosis when islets were cultured in 24·4 mM glucose concentration compared with untreated islets at the same glucose concentration (6·02 0·62% vs 4·44 0·63%; P<0·05). High glucose induced an increase in Fas expression in the islet cells, and this increase was maintained after cytokine or STZ treatment. However, the expression of anti-apoptotic mediators such as bcl-2 and bcl-xL did not show any significant change. These results suggest that cytokine-and STZmediated apoptotic effects on islet cells might be mediated by a glucose-induced hyperfunctional status and associated with an increase in Fas (Apo-1, CD-95) expression and no changes in the expression of the anti-apoptotic proteins bcl-xL and bcl-2.

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Section: Discussionmentioning

confidence: 38%

Section: Introductionmentioning

confidence: 99%

High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes

Mellado-Gil¹,

Diosdado²

2004

Journal of Endocrinology

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“…TRAF6 has been implicated in signaling via several receptors, including RANK (13,14), CD40 (53), IL-1R (18,54,55), TACI (56), BCMA (57), XEDAR (58,59), TROY (60), and CD14 (18). Several of these cytokines and lipopolysaccharide have been shown to induce apoptosis (61)(62)(63)(64). In addition, TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and lipopolysaccharide signaling (18).…”

Section: Discussionmentioning

confidence: 99%

Evidence That Receptor Activator of Nuclear Factor (NF)-κB Ligand Can Suppress Cell Proliferation and Induce Apoptosis through Activation of a NF-κB-independent and TRAF6-dependent Mechanism

Bharti

Takada

Shishodia

et al. 2004

Journal of Biological Chemistry

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The receptor activator of NF-B ligand (RANKL), a recently identified member of the tumor necrosis factor (TNF) superfamily, has been shown to induce osteoclastogenesis and dendritic cell survival. Most members of the TNF superfamily suppress cell proliferation and induce apoptosis, but whether RANKL does so is not known. We demonstrate that treatment of monocyte RAW 264.7 cells with RANKL induces dose-dependent growth inhibition (IC 50 ‫؍‬ 10 ng/ml) as determined by dye uptake and Human receptor activator of NF-B ligand (RANKL) 1 (TN-FSF11/TRANCE/OPGL/ODF), a cytokine independently discovered by four different groups (1-4), is a type II transmembrane protein of 317-amino acid length. It belongs to the TNF superfamily and has ϳ30% homology to the TNF-related apoptosis-inducing ligand (TRAIL) and to CD40L and about 20% homology to Fas ligand. It exists in two forms: a 40-to 45-kDa cellular form and a 31-kDa soluble form derived by cleavage of the full-length form at positions

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“…However, the mechanism of apoptosis in the non-infected cell is unknown. It has been demonstrated that cytokines, such as tumour necrosis factoralpha (TNF-a) [18], interferon-alpha (IFN-a) [28], interleukin (IL)-1 [6,11] and interleukin-10 [12,33] can induce apoptosis. A PRRSV infection generally fails to induce substantial amounts of IFN-a [1,30,32].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines

et al. 2003

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-Apoptosis was studied in the lungs of pigs during an infection with a European strain of porcine reproductive and respiratory syndrome virus (PRRSV) and it was examined if cytokines were involved in the induction of apoptosis. Twenty-two 4-to 5-week-old gnotobiotic pigs were inoculated intranasally with 10 6.0 TCID 50 of the Lelystad virus and euthanised between 1 and 52 days post inoculation (PI). The lungs and broncho-alveolar lavage (BAL) cells were assessed both for virus replication and apoptosis; BAL fluids were examined for interleukin (IL)-1, tumour necrosis factor-alpha and IL-10. Double-labellings were conducted to determine the relation between virus replication and apoptosis and to identify the apoptotic cells. Apoptosis occurred in both infected and non-infected cells. The percentages of infected cells, which were apoptotic, ranged between 9 and 39% in the lungs and between 13 and 30% in the BAL cells. The majority of apoptotic cells were non-infected. Non-infected apoptotic cells in the lungs were predominantly monocytes/macrophages, whereas those in the broncho-alveolar spaces were predominantly lymphocytes. The peak of apoptosis in the lungs at 14 days PI was preceded by a peak of IL-1 and IL-10 production at 9 days PI, suggesting a possible role of these cytokines in the induction of apoptosis in non-infected interstitial monocytes/macrophages. However, the latter hypothesis was not confirmed in vitro, since blood monocytes or alveolar macrophages did not undergo apoptosis after treatment with recombinant porcine IL-1 or IL-10. pig / lung / porcine reproductive and respiratory syndrome virus / apoptosis / cytokine

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Identification of Interleukin 1-induced Apoptosis in Rat Islets Usingin situSpecific Labelling of Fragmented DNA

Cited by 46 publications

References 0 publications

High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes

High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes

Evidence That Receptor Activator of Nuclear Factor (NF)-κB Ligand Can Suppress Cell Proliferation and Induce Apoptosis through Activation of a NF-κB-independent and TRAF6-dependent Mechanism

Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines

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