IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

M L B Jacobsen; S G Rønn; C Bruun; C M Larsen; D L Eizirik; T Mandrup-Poulsen; N Billestrup

doi:10.1007/s00125-008-1199-1

IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

M L B Jacobsen, S G Rønn, C Bruun, C M Larsen, D L Eizirik, T Mandrup-Poulsen, N Billestrup

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

21 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Feb

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	52
Udgave nummer	2
Sider (fra-til)	281-8
Antal sider	7
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-008-1199-1
Status	Udgivet - 2008

Bibliografisk note

Keywords: Animals; Cell Line; Chemokine CCL2; Chemokines; Insulin; Insulin-Secreting Cells; Interferon-gamma; Interleukin-1beta; RNA, Messenger; Rats; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Transcription, Genetic

Adgang til dokumentet

10.1007/s00125-008-1199-1

Citationsformater

@article{717dad0035a211df8ed1000ea68e967b,

title = "IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells",

abstract = "AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas mRNA expression. The ability of SOCS-3 to influence the activity of cytokine-responsive Fas and Mcp-1 (also known as Ccl2) promoters was measured by reporter analysis. RESULTS: IL-1beta induced a time-dependent increase in Mcp-1 and Mip-2 (also known as Cxcl2) mRNA expression after 6 h of stimulation in insulinoma (INS)-1 and neonatal rat islet cells. This induction was inhibited when Socs3 was expressed in the cells. In INS-1 cells, IL-1beta + IFN-gamma induced a tenfold and eightfold increase of Fas mRNA expression after 6 and 24 h, respectively. This induction was inhibited at both time-points when expression of Socs3 was induced. In promoter studies SOCS-3 significantly inhibited the cytokine-induced activity of Mcp-1 and Fas promoter constructs. CONCLUSIONS/INTERPRETATION: SOCS-3 inhibits the expression of cytokine-induced chemokine and death-receptor Fas mRNA.",

author = "Jacobsen, {M L B} and R{\o}nn, {S G} and C Bruun and Larsen, {C M} and Eizirik, {D L} and T Mandrup-Poulsen and N Billestrup",

note = "Keywords: Animals; Cell Line; Chemokine CCL2; Chemokines; Insulin; Insulin-Secreting Cells; Interferon-gamma; Interleukin-1beta; RNA, Messenger; Rats; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Transcription, Genetic",

year = "2008",

doi = "10.1007/s00125-008-1199-1",

language = "English",

volume = "52",

pages = "281--8",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "2",

}

TY - JOUR

T1 - IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

AU - Jacobsen, M L B

AU - Rønn, S G

AU - Bruun, C

AU - Larsen, C M

AU - Eizirik, D L

AU - Mandrup-Poulsen, T

AU - Billestrup, N

N1 - Keywords: Animals; Cell Line; Chemokine CCL2; Chemokines; Insulin; Insulin-Secreting Cells; Interferon-gamma; Interleukin-1beta; RNA, Messenger; Rats; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Transcription, Genetic

PY - 2008

Y1 - 2008

N2 - AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas mRNA expression. The ability of SOCS-3 to influence the activity of cytokine-responsive Fas and Mcp-1 (also known as Ccl2) promoters was measured by reporter analysis. RESULTS: IL-1beta induced a time-dependent increase in Mcp-1 and Mip-2 (also known as Cxcl2) mRNA expression after 6 h of stimulation in insulinoma (INS)-1 and neonatal rat islet cells. This induction was inhibited when Socs3 was expressed in the cells. In INS-1 cells, IL-1beta + IFN-gamma induced a tenfold and eightfold increase of Fas mRNA expression after 6 and 24 h, respectively. This induction was inhibited at both time-points when expression of Socs3 was induced. In promoter studies SOCS-3 significantly inhibited the cytokine-induced activity of Mcp-1 and Fas promoter constructs. CONCLUSIONS/INTERPRETATION: SOCS-3 inhibits the expression of cytokine-induced chemokine and death-receptor Fas mRNA.

AB - AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas mRNA expression. The ability of SOCS-3 to influence the activity of cytokine-responsive Fas and Mcp-1 (also known as Ccl2) promoters was measured by reporter analysis. RESULTS: IL-1beta induced a time-dependent increase in Mcp-1 and Mip-2 (also known as Cxcl2) mRNA expression after 6 h of stimulation in insulinoma (INS)-1 and neonatal rat islet cells. This induction was inhibited when Socs3 was expressed in the cells. In INS-1 cells, IL-1beta + IFN-gamma induced a tenfold and eightfold increase of Fas mRNA expression after 6 and 24 h, respectively. This induction was inhibited at both time-points when expression of Socs3 was induced. In promoter studies SOCS-3 significantly inhibited the cytokine-induced activity of Mcp-1 and Fas promoter constructs. CONCLUSIONS/INTERPRETATION: SOCS-3 inhibits the expression of cytokine-induced chemokine and death-receptor Fas mRNA.

U2 - 10.1007/s00125-008-1199-1

DO - 10.1007/s00125-008-1199-1

M3 - Journal article

C2 - 19002429

VL - 52

SP - 281

EP - 288

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 2

ER -