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

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Regulation of the beta-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. / 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.

In: Molecular and Cellular Endocrinology, Vol. 478, 2018, p. 106-114.

Research output: Contribution to journalJournal articleResearchpeer-review

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 beta-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., ... Mandrup-Poulsen, T. (2018). Regulation of the beta-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

Vancouver

Ghiasi SM, Dahllöf MS, Osmai Y, Osmai M, Jakobsen KK, Aivazidis A et al. Regulation of the beta-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. Molecular and Cellular Endocrinology. 2018;478:106-114. https://doi.org/10.1016/j.mce.2018.08.001

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 beta-cell inflammasome and contribution to stress-induced cellular dysfunction and apoptosis. In: Molecular and Cellular Endocrinology. 2018 ; Vol. 478. pp. 106-114.

Bibtex

@article{fd0dfbf193a14751b579b9dadc0bb013,
title = "Regulation of the beta-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.",
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 {\circledC} 2018. Published by Elsevier B.V.",
year = "2018",
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 beta-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

Y1 - 2018

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.

UR - http://www.scopus.com/inward/record.url?scp=85052079320&partnerID=8YFLogxK

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: 201419580