Poly(ADP-ribose) polymerase-1 modulates interferon-gamma-inducible protein (IP)-10 expression in murine embryonic fibroblasts by stabilizing IP-10 mRNA.
Mol Immunol
; 47(7-8): 1492-9, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20171739
ABSTRACT
Poly(ADP-ribose) polymerase-1 (Parp-1) is a nuclear enzyme that uses NAD(+) as a substrate to catalyze the addition of ADP-ribose polymers on a variety of nuclear proteins, modifying transiently their biological functions. Parp-1 has been involved in transcription regulation of many genes involved in the inflammatory response including cytokines and chemokines. Accordingly, genetic deletion of Parp-1 (Parp-1(-/-)) or pharmacological blockade of Parp-1 activity in mice results in a defective inflammatory immune response which confers an advantage in different pathophysiological conditions associated with inflammation. In addition to the transcriptional control, increasing mRNA stability, mainly through the mitogen-activated protein kinase p38 (p38(MAPK)) might be an important mechanism for the tight regulation in the expression of several chemokines such as IP-10. Here we demonstrate that Parp-1 deficiency in embryonic fibroblasts results in diminished IFN-gamma-induced IP-10 expression despite normal STAT1 activation and IP-10 promoter activity. Therefore, we have analyzed the involvement of Parp-1 in IP-10 mRNA stability. Parp-1 deficient cells showed a decreased half-life of IFN-gamma-induced IP-10 transcripts associated with a defect in p38(MAPK) activation. Our results demonstrate that Parp-1 can regulate inflammatory gene expression by increasing mRNA stability, via modulating a proper p38(MAPK) signalling pathway.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Regulación de la Expresión Génica
/
Poli(ADP-Ribosa) Polimerasas
/
Estabilidad del ARN
/
Quimiocina CXCL10
/
Fibroblastos
Límite:
Animals
Idioma:
En
Año:
2010
Tipo del documento:
Article