Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

Allan Ertman Karlsen; P E Heding; H Frobøse; S G Rønn; M Kruhøffer; T F Orntoft; M Darville; D L Eizirik; F Pociot; J Nerup; Thomas Mandrup-Poulsen; N Billestrup

doi:10.1007/s00125-004-1568-3

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

Allan Ertman Karlsen, P E Heding, H Frobøse, S G Rønn, M Kruhøffer, T F Orntoft, M Darville, D L Eizirik, F Pociot, J Nerup, Thomas Mandrup-Poulsen, N Billestrup

Endocrinology and Metabolism

45 Citations (Scopus)

Abstract

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.

Original language	English
Journal	Diabetologia
Volume	47
Issue number	11
Pages (from-to)	1998-2011
Number of pages	14
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-004-1568-3
Publication status	Published - 1 Nov 2004

Keywords

Animals
Apoptosis
Base Sequence
Cell Line
DNA Primers
Gene Expression Regulation
Interleukin-1
NF-kappa B
Nitric Oxide
Oligonucleotide Array Sequence Analysis
Rats
Repressor Proteins
Signal Transduction
Suppressor of Cytokine Signaling Proteins
Transcription Factors

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Karlsen, A. E., Heding, P. E., Frobøse, H., Rønn, S. G., Kruhøffer, M., Orntoft, T. F., Darville, M., Eizirik, D. L., Pociot, F., Nerup, J., Mandrup-Poulsen, T., & Billestrup, N. (2004). Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways. Diabetologia, 47(11), 1998-2011. https://doi.org/10.1007/s00125-004-1568-3

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways. / Karlsen, Allan Ertman; Heding, P E; Frobøse, H et al.

In: Diabetologia, Vol. 47, No. 11, 01.11.2004, p. 1998-2011.

Research output: Contribution to journal › Journal article › Research › peer-review

Karlsen, AE, Heding, PE, Frobøse, H, Rønn, SG, Kruhøffer, M, Orntoft, TF, Darville, M, Eizirik, DL, Pociot, F, Nerup, J, Mandrup-Poulsen, T & Billestrup, N 2004, 'Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways', Diabetologia, vol. 47, no. 11, pp. 1998-2011. https://doi.org/10.1007/s00125-004-1568-3

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abstract = "The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.",

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AU - Karlsen, Allan Ertman

AU - Heding, P E

AU - Frobøse, H

AU - Rønn, S G

AU - Kruhøffer, M

AU - Orntoft, T F

AU - Darville, M

AU - Eizirik, D L

AU - Pociot, F

AU - Nerup, J

AU - Mandrup-Poulsen, Thomas

AU - Billestrup, N

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N2 - The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.

AB - The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.

KW - Animals

KW - Apoptosis

KW - Base Sequence

KW - Cell Line

KW - DNA Primers

KW - Gene Expression Regulation

KW - Interleukin-1

KW - NF-kappa B

KW - Nitric Oxide

KW - Oligonucleotide Array Sequence Analysis

KW - Rats

KW - Repressor Proteins

KW - Signal Transduction

KW - Suppressor of Cytokine Signaling Proteins

KW - Transcription Factors

U2 - 10.1007/s00125-004-1568-3

DO - 10.1007/s00125-004-1568-3

M3 - Journal article

C2 - 15578154

SN - 0012-186X

VL - 47

SP - 1998

EP - 2011

JO - Diabetologia

JF - Diabetologia

IS - 11

ER -

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

Abstract

Keywords

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