期刊
MOLECULAR IMMUNOLOGY
卷 47, 期 7-8, 页码 1492-1499出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2010.01.022
关键词
IP-10; Parp-1; mRNA stability; p38(MAPK)
资金
- Spanish Ministerio de Ciencia e Innovacion [SAF2008-01572]
- Generalitat de Catalunya [2009/SGR/524]
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. (C) 2010 Elsevier Ltd. All rights reserved.
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