Significant and sustained activation of NF-кB during days 1-7 after PQ poisoning causes the release of inflammatory cytokines(TNF-α, IL-1β, IL-6, IL-10), initiating a cascade
effect and resulting in uncontrollable lung inflammation. In addition, large amounts of MDA were produced, which reduced free radical scavenger SOD and caused cell damage. Stem cell therapy has gained a great amount of attention in basic research and clinical application for treatment of lung injuries. Rojas et al.  found that bleomycin induces severe lung injury after ablation of mouse bone marrow, and exogenous BMSC transplantation significantly reduces lung inflammation. We found that BMSC transplantation significantly reduced Inhibitors,research,lifescience,medical NF-кB p65 expression in lung tissue after PQ poisoning, thus reducing the serum levels of TNF-α, IL-1β and IL-6 Inhibitors,research,lifescience,medical resulting in elevated IL-10 levels. In addition, transplantation of BMSCs also reduced MDA levels and SOD consumption, H 89 datasheet thereby lowering the wet/dry weight ratio of lungs after PQ poisoning. It has been suggested that BMSC reduce edema and exudation in lung injury, inhibit the release of inflammatory mediators and lipid peroxidation, attenuate inflammation and reduce cell damage. We also found that BMSC transplantation Inhibitors,research,lifescience,medical showed relatively weak efficacy in reducing NF-кB p65 on day 1 after PQ poisoning, which was consistent with the serum levels of TNF-α, IL-1β, IL-6 and IL-10, suggesting that BMSCs did not efficiently inhibit
the early inflammatory response. We speculate that the grafted BMSCs required time to be fully functional after transplantation and therefore were not effective during days 1–3 after Inhibitors,research,lifescience,medical PQ poising. However, BMSC transplantation maintained constant protection during days 7–14 after PQ poisoning. A number of cytokines and inflammatory mediators Inhibitors,research,lifescience,medical attract transplanted BMSC, but are also toxic and may compromise the survival of BMSC. It has been shown that TNF-α neutralization decreases the incidence of lung injury in mice after bone marrow transplantation [15,16]. High-dose MP is widely used to treat PQ poisoning because of its potent anti-inflammatory
effects and ability to improve early lung injury. However, the use of corticosteroids found does not reduce mortality after PQ poisoning . In this study, we showed that during days 1–3 after PQ poisoning, treatment with MP alone was superior to that of BMSC transplantation to reduce NF-кB p65 expression in lung tissue, lower serum levels of IL-1β, TNF-, and IL-6, increase IL-10 levels, inhibit MDA production and SOD consumption and lower the wet/dry weight ratio of lungs. However, the efficacy of MP to treat lung injury gradually decreased on days 1–7 after PQ poisoning, which may explain why high-dose MP improves the symptoms of PQ poisoning, but does not reduce mortality. The efficacy of BMSC transplantation combined with MP for the treatment of PQ-induced lung injury was investigated in this study.