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IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells.
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- معلومة اضافية
- Publisher Information:
2009
- نبذة مختصرة :
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.
Journal Article
Research Support, Non-U.S. Gov't
info:eu-repo/semantics/published
- الموضوع:
- Availability:
Open access content. Open access content
1 full-text file(s): info:eu-repo/semantics/restrictedAccess
- Note:
1 full-text file(s): application/pdf
English
- Other Numbers:
EQY oai:dipot.ulb.ac.be:2013/52506
uri/info:doi/10.1007/s00125-008-1199-1
uri/info:pmid/19002429
uri/info:scp/58149456481
1363711955
- Contributing Source:
UNIVERSITE LIBRE DE BRUXELLES
From OAIster®, provided by the OCLC Cooperative.
- الرقم المعرف:
edsoai.on1363711955
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