TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells

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Standard

TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells. / Prause, Michala; Berchtold, Lukas Adrian; Urizar, Adriana Ibarra; Trauelsen, Mette; Billestrup, Nils; Mandrup-Poulsen, Thomas; Størling, Joachim.

I: Molecular and Cellular Endocrinology, Bind 420, 15.01.2016, s. 24-36.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Prause, M, Berchtold, LA, Urizar, AI, Trauelsen, M, Billestrup, N, Mandrup-Poulsen, T & Størling, J 2016, 'TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells', Molecular and Cellular Endocrinology, bind 420, s. 24-36. https://doi.org/10.1016/j.mce.2015.11.021

APA

Prause, M., Berchtold, L. A., Urizar, A. I., Trauelsen, M., Billestrup, N., Mandrup-Poulsen, T., & Størling, J. (2016). TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells. Molecular and Cellular Endocrinology, 420, 24-36. https://doi.org/10.1016/j.mce.2015.11.021

Vancouver

Prause M, Berchtold LA, Urizar AI, Trauelsen M, Billestrup N, Mandrup-Poulsen T o.a. TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells. Molecular and Cellular Endocrinology. 2016 jan. 15;420:24-36. https://doi.org/10.1016/j.mce.2015.11.021

Author

Prause, Michala ; Berchtold, Lukas Adrian ; Urizar, Adriana Ibarra ; Trauelsen, Mette ; Billestrup, Nils ; Mandrup-Poulsen, Thomas ; Størling, Joachim. / TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells. I: Molecular and Cellular Endocrinology. 2016 ; Bind 420. s. 24-36.

Bibtex

@article{82fe78df69be4ffdbc58241b083f8bbc,

title = "TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells",

abstract = "Interleukin-1β (IL-1β) and interferon-γ (IFNγ) contribute to type 1 diabetes (T1D) by inducing β-cell death. Tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins are adaptors that transduce signaling from a variety of membrane receptors including cytokine receptors. We show here that IL-1β and IFNγ upregulate the expression of TRAF2 in insulin-producing INS-1E cells and isolated rat pancreatic islets. siRNA-mediated knockdown (KD) of TRAF2 in INS-1E cells reduced IL-1β-induced phosphorylation of JNK1/2, but not of p38 or ERK1/2 mitogen-activated protein kinases. TRAF2 KD did not modulate NFκB activation by cytokines, but reduced cytokine-induced inducible nitric oxide synthase (iNOS) promotor activity and expression. We further observed that IFNγ-stimulated phosphorylation of STAT3 required TRAF2. KD of TRAF2 or STAT3 reduced cytokine-induced caspase 3/7 activation, but, intriguingly, potentiated cytokine-mediated loss of plasma membrane integrity and augmented the number of propidium iodide-positive cells. Finally, we found that TRAF2 KD increased cytokine-induced production of reactive oxygen species (ROS). In summary, our data suggest that TRAF2 is an important mediator of IL-1β and IFNγ signaling in pancreatic β-cells.",

author = "Michala Prause and Berchtold, {Lukas Adrian} and Urizar, {Adriana Ibarra} and Mette Trauelsen and Nils Billestrup and Thomas Mandrup-Poulsen and Joachim St{\o}rling",

year = "2016",

month = jan,

day = "15",

doi = "10.1016/j.mce.2015.11.021",

language = "English",

volume = "420",

pages = "24--36",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - TRAF2 mediates JNK and STAT3 activation in response to IL-1β and IFNγ and facilitates apoptotic death of insulin-producing β-cells

AU - Prause, Michala

AU - Berchtold, Lukas Adrian

AU - Urizar, Adriana Ibarra

AU - Trauelsen, Mette

AU - Billestrup, Nils

AU - Mandrup-Poulsen, Thomas

AU - Størling, Joachim

PY - 2016/1/15

Y1 - 2016/1/15

N2 - Interleukin-1β (IL-1β) and interferon-γ (IFNγ) contribute to type 1 diabetes (T1D) by inducing β-cell death. Tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins are adaptors that transduce signaling from a variety of membrane receptors including cytokine receptors. We show here that IL-1β and IFNγ upregulate the expression of TRAF2 in insulin-producing INS-1E cells and isolated rat pancreatic islets. siRNA-mediated knockdown (KD) of TRAF2 in INS-1E cells reduced IL-1β-induced phosphorylation of JNK1/2, but not of p38 or ERK1/2 mitogen-activated protein kinases. TRAF2 KD did not modulate NFκB activation by cytokines, but reduced cytokine-induced inducible nitric oxide synthase (iNOS) promotor activity and expression. We further observed that IFNγ-stimulated phosphorylation of STAT3 required TRAF2. KD of TRAF2 or STAT3 reduced cytokine-induced caspase 3/7 activation, but, intriguingly, potentiated cytokine-mediated loss of plasma membrane integrity and augmented the number of propidium iodide-positive cells. Finally, we found that TRAF2 KD increased cytokine-induced production of reactive oxygen species (ROS). In summary, our data suggest that TRAF2 is an important mediator of IL-1β and IFNγ signaling in pancreatic β-cells.

AB - Interleukin-1β (IL-1β) and interferon-γ (IFNγ) contribute to type 1 diabetes (T1D) by inducing β-cell death. Tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins are adaptors that transduce signaling from a variety of membrane receptors including cytokine receptors. We show here that IL-1β and IFNγ upregulate the expression of TRAF2 in insulin-producing INS-1E cells and isolated rat pancreatic islets. siRNA-mediated knockdown (KD) of TRAF2 in INS-1E cells reduced IL-1β-induced phosphorylation of JNK1/2, but not of p38 or ERK1/2 mitogen-activated protein kinases. TRAF2 KD did not modulate NFκB activation by cytokines, but reduced cytokine-induced inducible nitric oxide synthase (iNOS) promotor activity and expression. We further observed that IFNγ-stimulated phosphorylation of STAT3 required TRAF2. KD of TRAF2 or STAT3 reduced cytokine-induced caspase 3/7 activation, but, intriguingly, potentiated cytokine-mediated loss of plasma membrane integrity and augmented the number of propidium iodide-positive cells. Finally, we found that TRAF2 KD increased cytokine-induced production of reactive oxygen species (ROS). In summary, our data suggest that TRAF2 is an important mediator of IL-1β and IFNγ signaling in pancreatic β-cells.

U2 - 10.1016/j.mce.2015.11.021

DO - 10.1016/j.mce.2015.11.021

M3 - Journal article

C2 - 26610752

VL - 420

SP - 24

EP - 36

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -

ID: 164621516