system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Cecum, Cell Line, Disease Models, Animal, Ligation, Lipopolysaccharides, Liver, Macrophages, Male, Membrane Microdomains, Membrane Proteins, Mice, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, Nitric Oxide, Nitric Oxide Synthase Type II, Punctures, RNA-Binding Proteins, Reactive Oxygen Species, Sepsis, Sequence Deletion, Signal Transduction, Specific Pathogen-Free Organisms, Toll-Like Receptor 4.
user
Does suppression of PTRF alleviate the polymicrobial sepsis induced by cecal ligation and puncture in mice? Context: 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. 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. 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.
assistant
PTRF is a crucial regulator of TLR4 signaling in the development of sepsis. Final Decision: yes