| First Author | von Knethen A | Year | 2011 |
| Journal | Free Radic Biol Med | Volume | 51 |
| Issue | 2 | Pages | 396-405 |
| PubMed ID | 21571064 | Mgi Jnum | J:174098 |
| Mgi Id | MGI:5051884 | Doi | 10.1016/j.freeradbiomed.2011.04.033 |
| Citation | von Knethen A, et al. (2011) PPARgamma stabilizes HO-1 mRNA in monocytes/macrophages which affects IFN-beta expression. Free Radic Biol Med 51(2):396-405 |
| abstractText | NADPH oxidase activation in either RAW264.7 cells or peritoneal macrophages (PM) derived from PPARgamma wild-type mice increased reactive oxygen species (ROS) formation, caused PPARgamma activation, heme oxygenase-1 (HO-1) induction, and concomitant IFN-beta expression. In macrophages transduced with a dominant negative (d/n) mutant of PPARgamma (RAW264.7 AF2) as well as PPARgamma negative PM derived from Mac-PPARgamma-KO mice, NADPH oxidase-dependent IFN-beta expression was attenuated. As the underlying mechanism, we noted decreased HO-1 mRNA stability in RAW264.7 AF2 cells as well as PPARgamma negative PM, compared to either parent RAW264.7 cells or wild-type PM. Assuming mRNA stabilization of HO-1 by PPARgamma we transfected macrophages with a HO-1 3'-UTR reporter construct. The PPARgamma agonist rosiglitazone significantly up-regulated luciferase expression in RAW264.7 cells, while it remained unaltered in RAW264.7 AF2 macrophages. Deletion of each of two AU-rich elements in the 3'-UTR HO-1 decreased luciferase activity in RAW264.7 cells. Using LPS as a NADPH oxidase activator, PM from Mac-PPARgamma-KO mice showed a decreased HO-1 mRNA half-life in vitro and in vivo compared to PPARgamma wild-type mice. These data identified a so far unappreciated role of PPARgamma in stabilizing HO-1 mRNA, thus, contributing to the expression of the HO-1 target gene IFN-beta. |
