| First Author | Galbis-Martínez M | Year | 2010 |
| Journal | Mol Immunol | Volume | 47 |
| Issue | 7-8 | Pages | 1492-9 |
| PubMed ID | 20171739 | Mgi Jnum | J:160646 |
| Mgi Id | MGI:4454757 | Doi | 10.1016/j.molimm.2010.01.022 |
| Citation | Galbis-Martinez M, et al. (2010) 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 |
| abstractText | 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. |
