The immunoproteasome is induced by cytokines and regulates apoptosis in human islets

Research output: Contribution to journalJournal articleResearchpeer-review

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The immunoproteasome is induced by cytokines and regulates apoptosis in human islets. / Lundh, Morten; Bugliani, Marco; Dahlby, Tina; Chou, Danny Hung-Chieh; Wagner , Bridget; Ghiasi, Seyed Mojtaba; De Tata, Vincenzo; Chen, Zhifei; Lund, Marianne Nissen; Davies, Michael Jonathan; Marchetti, Piero; Mandrup-Poulsen, Thomas.

In: Journal of Endocrinology, Vol. 233, No. 3, 2017, p. 369-379.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lundh, M, Bugliani, M, Dahlby, T, Chou, DH-C, Wagner , B, Ghiasi, SM, De Tata, V, Chen, Z, Lund, MN, Davies, MJ, Marchetti, P & Mandrup-Poulsen, T 2017, 'The immunoproteasome is induced by cytokines and regulates apoptosis in human islets', Journal of Endocrinology, vol. 233, no. 3, pp. 369-379. https://doi.org/10.1530/JOE-17-0110

APA

Lundh, M., Bugliani, M., Dahlby, T., Chou, D. H-C., Wagner , B., Ghiasi, S. M., ... Mandrup-Poulsen, T. (2017). The immunoproteasome is induced by cytokines and regulates apoptosis in human islets. Journal of Endocrinology, 233(3), 369-379. https://doi.org/10.1530/JOE-17-0110

Vancouver

Lundh M, Bugliani M, Dahlby T, Chou DH-C, Wagner B, Ghiasi SM et al. The immunoproteasome is induced by cytokines and regulates apoptosis in human islets. Journal of Endocrinology. 2017;233(3):369-379. https://doi.org/10.1530/JOE-17-0110

Author

Lundh, Morten ; Bugliani, Marco ; Dahlby, Tina ; Chou, Danny Hung-Chieh ; Wagner , Bridget ; Ghiasi, Seyed Mojtaba ; De Tata, Vincenzo ; Chen, Zhifei ; Lund, Marianne Nissen ; Davies, Michael Jonathan ; Marchetti, Piero ; Mandrup-Poulsen, Thomas. / The immunoproteasome is induced by cytokines and regulates apoptosis in human islets. In: Journal of Endocrinology. 2017 ; Vol. 233, No. 3. pp. 369-379.

Bibtex

@article{58a60ffed2354a2a92ede07831fa08a2,
title = "The immunoproteasome is induced by cytokines and regulates apoptosis in human islets",
abstract = "In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E and human islets exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules, we assessed the role of the immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines induce the expression and activity of the immuno-proteasome in INS-1E cells and human islets. Cytokine-induced expression of immuno-proteasome subunits, but not activity, depended upon histone deacetylase 3 activation. Inhibition of JAK1/STAT1 signaling did not affect proteasomal activity. Inhibition of the immuno-proteasome subunit PSMB8 aggravated cytokine-induced human beta-cell apoptosis while reducing intracellular levels of oxidized proteins in INS-1 cells. While cytokines increased total cellular NFκB subunit P50 and P52 levels and reduced the cytosolic NFκB subunit P65 and IκB levels, these effects were unaffected by PSMB8 inhibition. We conclude that beta cells upregulate immuno-proteasome expression and activity in response to IFNγ, likely as a protective response to confine inflammatory signaling.",
author = "Morten Lundh and Marco Bugliani and Tina Dahlby and Chou, {Danny Hung-Chieh} and Bridget Wagner and Ghiasi, {Seyed Mojtaba} and {De Tata}, Vincenzo and Zhifei Chen and Lund, {Marianne Nissen} and Davies, {Michael Jonathan} and Piero Marchetti and Thomas Mandrup-Poulsen",
year = "2017",
doi = "10.1530/JOE-17-0110",
language = "English",
volume = "233",
pages = "369--379",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "BioScientifica Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - The immunoproteasome is induced by cytokines and regulates apoptosis in human islets

AU - Lundh, Morten

AU - Bugliani, Marco

AU - Dahlby, Tina

AU - Chou, Danny Hung-Chieh

AU - Wagner , Bridget

AU - Ghiasi, Seyed Mojtaba

AU - De Tata, Vincenzo

AU - Chen, Zhifei

AU - Lund, Marianne Nissen

AU - Davies, Michael Jonathan

AU - Marchetti, Piero

AU - Mandrup-Poulsen, Thomas

PY - 2017

Y1 - 2017

N2 - In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E and human islets exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules, we assessed the role of the immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines induce the expression and activity of the immuno-proteasome in INS-1E cells and human islets. Cytokine-induced expression of immuno-proteasome subunits, but not activity, depended upon histone deacetylase 3 activation. Inhibition of JAK1/STAT1 signaling did not affect proteasomal activity. Inhibition of the immuno-proteasome subunit PSMB8 aggravated cytokine-induced human beta-cell apoptosis while reducing intracellular levels of oxidized proteins in INS-1 cells. While cytokines increased total cellular NFκB subunit P50 and P52 levels and reduced the cytosolic NFκB subunit P65 and IκB levels, these effects were unaffected by PSMB8 inhibition. We conclude that beta cells upregulate immuno-proteasome expression and activity in response to IFNγ, likely as a protective response to confine inflammatory signaling.

AB - In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E and human islets exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules, we assessed the role of the immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines induce the expression and activity of the immuno-proteasome in INS-1E cells and human islets. Cytokine-induced expression of immuno-proteasome subunits, but not activity, depended upon histone deacetylase 3 activation. Inhibition of JAK1/STAT1 signaling did not affect proteasomal activity. Inhibition of the immuno-proteasome subunit PSMB8 aggravated cytokine-induced human beta-cell apoptosis while reducing intracellular levels of oxidized proteins in INS-1 cells. While cytokines increased total cellular NFκB subunit P50 and P52 levels and reduced the cytosolic NFκB subunit P65 and IκB levels, these effects were unaffected by PSMB8 inhibition. We conclude that beta cells upregulate immuno-proteasome expression and activity in response to IFNγ, likely as a protective response to confine inflammatory signaling.

U2 - 10.1530/JOE-17-0110

DO - 10.1530/JOE-17-0110

M3 - Journal article

C2 - 28438776

VL - 233

SP - 369

EP - 379

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 3

ER -

ID: 178799094