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

Abstract

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. 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. 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. 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. 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.