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IL-1β-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells.
- Source :
- Diabetologia; Feb2009, Vol. 52 Issue 2, p281-288, 8p, 6 Graphs
- Publication Year :
- 2009
-
Abstract
- 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-1β and IFN-γ 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-1β- and IFN-γ-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. 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. IL-1β 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-1β + IFN-γ 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. SOCS-3 inhibits the expression of cytokine-induced chemokine and death-receptor Fas mRNA. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0012186X
- Volume :
- 52
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 35997082
- Full Text :
- https://doi.org/10.1007/s00125-008-1199-1