Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-κB Signaling Pathway Inhibition.

ABSTRACT

Bone marrow mesenchymal stromal cells (BMSCs) have positive therapeutic effects on inflammation associated diseases. However, the underlying mechanism is largely unknown. This study was conducted to investigate whether BMSCs could alleviate the inflammation reaction in lipopolysaccaride (LPS)-induced acute kidney injury (septic-AKI) of rats via inhibition of toll-like receptors (TLR4)-nuclear factor-kappa B (NF-κB) signaling pathway. The septic-AKI rat model was established by injecting the 1ml/mg LPS through the femoral vein. Based on this model, rats were subjected to BMSC transplantation, PDTC (a kind of NF-κB inhibitor) administration alone, and combined treatment of the first two together. Results showed that LPS treatment caused the increases of the concentration of blood urea nitrogen (BUN) and serum creatinine (SCr), accompanied by tissue injury and the up-regulation of TLR4 and NF-κB, that was its key downstream signaling molecule, in both mRNA and protein level. Notably, it has been found that BMSCs transplantation significantly reversed the already upregulated concentration of BUN and SCr, dramatically attenuated the event of the tissue injury, and prominently reduced mortality after AKI. These were paralleled by down-regulation of the level of TLR4 and NF-κB. These effects of BMSCs transplantation were similar to those of PDTC treatment. Importantly, the effects in the combination therapy of BMSCs transplantation and PDTC group were much stronger than those of either BMSCs or PDTC used alone. These findings suggest that BMSCs transplantation contributes to therapeutic effects in LPS-induced AKI rat model, and that the most obvious effects occurred in the combined treatment group, with BMSCs and PDTC together, which was tightly associated with inhibition of the TLR4-NF-κB signaling pathway.