| First Author | Zheng Y | Year | 2013 |
| Journal | J Infect Dis | Volume | 208 |
| Issue | 11 | Pages | 1803-12 |
| PubMed ID | 23908488 | Mgi Jnum | J:328496 |
| Mgi Id | MGI:6872637 | Doi | 10.1093/infdis/jit364 |
| Citation | Zheng Y, et al. (2013) Suppression of PTRF alleviates the polymicrobial sepsis induced by cecal ligation and puncture in mice. J Infect Dis 208(11):1803-12 |
| abstractText | BACKGROUND: Sepsis and sepsis-associated organ failure are devastating conditions. Understanding the detailed cellular/molecular mechanisms involved in sepsis should lead to the identification of novel therapeutic targets. METHODS: Cecal ligation and puncture (CLP) was used as a polymicrobial sepsis model in vivo to determine mortality and end-organ damage. Macrophages were adopted as the cellular model in vitro for mechanistic studies. RESULTS: PTRF+/- mice survived longer and suffered less organ damage after CLP. Reductions in nitric oxide (NO) and iNOS biosynthesis were observed in plasma, macrophages, and vital organs in the PTRF+/- mice. Using an acute sepsis model after CLP, we found that iNOS-/- mice had a comparable level of survival as the PTRF+/- mice. Similarly, polymerase I transcript release factor (PTRF) deficiency resulted in decreased iNOS and NO/ROS production in macrophages in vitro. Mechanistically, lipopolysaccharide (LPS) enhanced the co-localization and interaction between PTRF and TLR4 in lipid rafts. Deletion of PTRF blocked formation of the TLR4/Myd88 complex after LPS. Consistent with this, lack of PTRF impaired the TLR4 signaling, as shown by the decreased p-JNK, p-ERK, and p-p38, which are upstream factors involved in iNOS transcription. CONCLUSION: PTRF is a crucial regulator of TLR4 signaling in the development of sepsis. |
