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Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis

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Harvard

Ghiasi, SM, Dahllöf, MS, Osmai, Y, Osmai, M, Jakobsen, KK, Aivazidis, A, Tyrberg, B, Perruzza, L, Prause, MCB, Christensen, DP, Fog-Tonnesen, M, Lundh, M, Grassi, F, Chatenoud, L & Mandrup-Poulsen, T 2018, 'Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis', Molecular and Cellular Endocrinology, vol. 478, pp. 106-114. https://doi.org/10.1016/j.mce.2018.08.001

APA

Ghiasi, S. M., Dahllöf, M. S., Osmai, Y., Osmai, M., Jakobsen, K. K., Aivazidis, A., Tyrberg, B., Perruzza, L., Prause, M. C. B., Christensen, D. P., Fog-Tonnesen, M., Lundh, M., Grassi, F., Chatenoud, L., & Mandrup-Poulsen, T. (2018). Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. Molecular and Cellular Endocrinology, 478, 106-114. https://doi.org/10.1016/j.mce.2018.08.001

CBE

Ghiasi SM, Dahllöf MS, Osmai Y, Osmai M, Jakobsen KK, Aivazidis A, Tyrberg B, Perruzza L, Prause MCB, Christensen DP, Fog-Tonnesen M, Lundh M, Grassi F, Chatenoud L, Mandrup-Poulsen T. 2018. Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. Molecular and Cellular Endocrinology. 478:106-114. https://doi.org/10.1016/j.mce.2018.08.001

MLA

Vancouver

Author

Ghiasi, Seyed Mojtaba ; Dahllöf, Mattias Salling ; Osmai, Yama ; Osmai, Mirwais ; Jakobsen, Kathrine Kronberg ; Aivazidis, Alexander ; Tyrberg, Björn ; Perruzza, Lisa ; Prause, Michala Cecilie Burstein ; Christensen, Dan Ploug ; Fog-Tonnesen, Morten ; Lundh, Morten ; Grassi, Fabio ; Chatenoud, Lucienne ; Mandrup-Poulsen, Thomas. / Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. In: Molecular and Cellular Endocrinology. 2018 ; Vol. 478. pp. 106-114.

Bibtex

@article{ca88150e3a6f44a2a97bc5a21e9a6333,
title = "Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis",
abstract = "β-Cells may be a source of IL-1β that is produced as inactive pro-IL-1β and processed into biologically-active IL-1β by enzymatic cleavage mediated by the NLRP1-, NLRP3- and NLRC4-inflammasomes. Little is known about the β-cell inflammasomes. NLRP1-expression was upregulated in islet-cells from T2D-patients and by IL-1β+IFNγ in INS-1 cells in a histone-deacetylase dependent manner. NLRP3 was downregulated by cytokines in INS-1 cells. NLRC4 was barely expressed and not regulated by cytokines. High extracellular K+ reduced cytokine-induced apoptosis and NO production and restored cytokine-inhibited accumulated insulin-secretion. Basal inflammasome expression was JNK1-3 dependent. Knock-down of the ASC interaction domain common for NLRP1 and 3 improved insulin secretion and ameliorated IL-1β and/or glucolipotoxicity-induced cell death and reduced cytokine-induced NO-production. Broad inflammasome-inhibition, but not NLRP3-selective inhibition, protected against IL-1β-induced INS-1 cell-toxicity. We suggest that IL-1β causes β-cell toxicity in part by NLRP1 mediated caspase-1-activation and maturation of IL-1β leading to an autocrine potentiation loop.",
keywords = "Animals, Apoptosis/drug effects, CARD Signaling Adaptor Proteins, Cell Death/drug effects, Cell Line, Cytokines/pharmacology, Cytoprotection/drug effects, Female, Glucose/toxicity, Histone Deacetylases/metabolism, Humans, Inflammasomes/metabolism, Insulin Secretion/drug effects, Insulin-Secreting Cells/drug effects, Interleukin-1beta/metabolism, JNK Mitogen-Activated Protein Kinases/metabolism, Lipids/toxicity, Middle Aged, Potassium/pharmacology, RNA, Messenger/genetics, Rats, Receptors, Purinergic P2X7/metabolism, Stress, Physiological/drug effects, Young Adult",
author = "Ghiasi, {Seyed Mojtaba} and Dahll{\"o}f, {Mattias Salling} and Yama Osmai and Mirwais Osmai and Jakobsen, {Kathrine Kronberg} and Alexander Aivazidis and Bj{\"o}rn Tyrberg and Lisa Perruzza and Prause, {Michala Cecilie Burstein} and Christensen, {Dan Ploug} and Morten Fog-Tonnesen and Morten Lundh and Fabio Grassi and Lucienne Chatenoud and Thomas Mandrup-Poulsen",
note = "Copyright {\textcopyright} 2018. Published by Elsevier B.V.",
year = "2018",
month = dec,
day = "15",
doi = "10.1016/j.mce.2018.08.001",
language = "English",
volume = "478",
pages = "106--114",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Regulation of the β-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis

AU - Ghiasi, Seyed Mojtaba

AU - Dahllöf, Mattias Salling

AU - Osmai, Yama

AU - Osmai, Mirwais

AU - Jakobsen, Kathrine Kronberg

AU - Aivazidis, Alexander

AU - Tyrberg, Björn

AU - Perruzza, Lisa

AU - Prause, Michala Cecilie Burstein

AU - Christensen, Dan Ploug

AU - Fog-Tonnesen, Morten

AU - Lundh, Morten

AU - Grassi, Fabio

AU - Chatenoud, Lucienne

AU - Mandrup-Poulsen, Thomas

N1 - Copyright © 2018. Published by Elsevier B.V.

PY - 2018/12/15

Y1 - 2018/12/15

N2 - β-Cells may be a source of IL-1β that is produced as inactive pro-IL-1β and processed into biologically-active IL-1β by enzymatic cleavage mediated by the NLRP1-, NLRP3- and NLRC4-inflammasomes. Little is known about the β-cell inflammasomes. NLRP1-expression was upregulated in islet-cells from T2D-patients and by IL-1β+IFNγ in INS-1 cells in a histone-deacetylase dependent manner. NLRP3 was downregulated by cytokines in INS-1 cells. NLRC4 was barely expressed and not regulated by cytokines. High extracellular K+ reduced cytokine-induced apoptosis and NO production and restored cytokine-inhibited accumulated insulin-secretion. Basal inflammasome expression was JNK1-3 dependent. Knock-down of the ASC interaction domain common for NLRP1 and 3 improved insulin secretion and ameliorated IL-1β and/or glucolipotoxicity-induced cell death and reduced cytokine-induced NO-production. Broad inflammasome-inhibition, but not NLRP3-selective inhibition, protected against IL-1β-induced INS-1 cell-toxicity. We suggest that IL-1β causes β-cell toxicity in part by NLRP1 mediated caspase-1-activation and maturation of IL-1β leading to an autocrine potentiation loop.

AB - β-Cells may be a source of IL-1β that is produced as inactive pro-IL-1β and processed into biologically-active IL-1β by enzymatic cleavage mediated by the NLRP1-, NLRP3- and NLRC4-inflammasomes. Little is known about the β-cell inflammasomes. NLRP1-expression was upregulated in islet-cells from T2D-patients and by IL-1β+IFNγ in INS-1 cells in a histone-deacetylase dependent manner. NLRP3 was downregulated by cytokines in INS-1 cells. NLRC4 was barely expressed and not regulated by cytokines. High extracellular K+ reduced cytokine-induced apoptosis and NO production and restored cytokine-inhibited accumulated insulin-secretion. Basal inflammasome expression was JNK1-3 dependent. Knock-down of the ASC interaction domain common for NLRP1 and 3 improved insulin secretion and ameliorated IL-1β and/or glucolipotoxicity-induced cell death and reduced cytokine-induced NO-production. Broad inflammasome-inhibition, but not NLRP3-selective inhibition, protected against IL-1β-induced INS-1 cell-toxicity. We suggest that IL-1β causes β-cell toxicity in part by NLRP1 mediated caspase-1-activation and maturation of IL-1β leading to an autocrine potentiation loop.

KW - Animals

KW - Apoptosis/drug effects

KW - CARD Signaling Adaptor Proteins

KW - Cell Death/drug effects

KW - Cell Line

KW - Cytokines/pharmacology

KW - Cytoprotection/drug effects

KW - Female

KW - Glucose/toxicity

KW - Histone Deacetylases/metabolism

KW - Humans

KW - Inflammasomes/metabolism

KW - Insulin Secretion/drug effects

KW - Insulin-Secreting Cells/drug effects

KW - Interleukin-1beta/metabolism

KW - JNK Mitogen-Activated Protein Kinases/metabolism

KW - Lipids/toxicity

KW - Middle Aged

KW - Potassium/pharmacology

KW - RNA, Messenger/genetics

KW - Rats

KW - Receptors, Purinergic P2X7/metabolism

KW - Stress, Physiological/drug effects

KW - Young Adult

U2 - 10.1016/j.mce.2018.08.001

DO - 10.1016/j.mce.2018.08.001

M3 - Journal article

C2 - 30121202

VL - 478

SP - 106

EP - 114

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -

ID: 59692775