Attenuation of Lipopolysaccharide-induced Liver Injury by Bone Marrow Mesenchymal Stem Cells via Inhibiting the NLRP3 Inflammasome and Hepatocyte Pyroptosis

Abstract

Background: The transplantation of bone marrow mesenchymal cells (BMSCs) has been shown to be an effective mean for treating sepsis-related organ damage. Pytoptotic cell death, in turn, has recently been identified as a key driver of sepsis-related damage. At present, there are few studies on the effect of BMSC transplantation on pyroptotic cell death. Objective: We explored the ability of BMSCs to attenuate hepatic damage in a pyroptosis-related manner in a rat model of lipopolysaccharide (LPS)-induced liver injury. Methods: Following injury modeling and BMSC transplantation, we assessed the expression of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome, and key downstream pyroptosis-related signaling molecules. Results: It was found that BMSC transplantation was sufficient to significantly improve rat survival after LPS injection. A significantly reduced expression of the pyroptosis-related proteins NLRP3, caspase-1, IL-1β, and IL-18 in rats that had undergone BMSC transplantation compared to control animals was observed. Notably, this activity was superior to single-agent administration of the NLRP3 inhibitor MCC950. Conclusion: Our data suggest that BMSC transplantation may alleviate LPS-induced hepatic damage by suppressing the activation of the NLRP3 inflammasome and the induction of pyroptotic cell death.