Inhibitory effects of interferon-gamma on activation of rat pancreatic stellate cells are mediated by STAT1 and involve down-regulation of CTGF expression.
Cell Signal
; 19(4): 782-90, 2007 Apr.
Article
in En
| MEDLINE
| ID: mdl-17116388
ABSTRACT
Pancreatic stellate cells (PSCs) are the main source of extracellular matrix proteins in pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Interferon-gamma (IFN-gamma) is an antifibrotic cytokine, but how precisely it exerts its effects on PSCs is largely unknown. Here, we have focussed on the role of STAT1 as well as target genes of IFN-gamma signalling. Our data indicate that IFN-gamma regulates the expression of two autocrine mediators of PSC activation, connective tissue growth factor and endothelin-1, in a transforming growth factor-beta1-antagonistic manner. STAT1 overexpression under the control of a tetracycline-dependent promoter revealed a close correlation between STAT1 expression and activation, the biological effects of IFN-gamma (growth inhibition, induction of apoptosis), and target gene expression. Our data further support the hypothesis that IFN-gamma interferes with stellate cell activation in the pancreas and suggest activated STAT1 as an inductor of a quiescent PSC phenotype.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreas
/
Down-Regulation
/
Interferon-gamma
/
Immediate-Early Proteins
/
Intercellular Signaling Peptides and Proteins
/
STAT1 Transcription Factor
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Signal
Year:
2007
Document type:
Article
Affiliation country:
Alemania