Mesenchymal stem cell-conditioned medium induces neutrophils apoptosis via inhibition of NF-kB pathway and increases endogenous pulmonary stem cells in endotoxin-induced acute lung injury

Abstract

Introduction: The mechanism of Mesenchymal stem cells (MSCs) involving in acute lung injury (ALI) remains unknown. Aims and objectives: We investigated the effect of mesenchymal stem cell-conditioned medium (MSC-CM) in moderating the neutrophils apoptosis of endotoxin-induced ALI. Methods: Mouse MSC-CM were delivered through the tail veins of mice 4 hours after intratracheal instillation of endotoxin. Lung histopathological findings and the level of cytokines and the expression of endogenous stem cells of lung were analyzed at the end of 24 hours. Results: MSC-CM significantly diminished the histopathological changes of ALI and the numbers and activity of neutrophils in lung in comparison with controls. MSC-CM therapy reduces the levels of interleukin-6, macrophage inflammatory protein-2, myeloperoxidase and the expression of NF-kB p65 & phospho-NF-kB p65 in the lung of ALI mice. MSC-CM mediated a neutrophils apoptosis (reducing B-cell lymphoma-extra large (Bcl-xl) & Myeloid cell leukemia 1 (Mcl-1) expression on neutrophils), which were also confirmed by in human neutrophils (reducing NF-kB & matrix metallopeptidase-9 in peripheral-blood neutrophils from ARDS patients). In addition, MSC-CM enhanced the numbers of endogenous stem cells of lung. Conclusions: MSC-CM provides a beneficial effect to promote the neutrophils apoptosis and reduce the chemokines in endotoxin-induced ALI, which in partly is mediated by an suppression in NF-kB activity and reduction in Bcl-xl & Mcl-1expression. The endogenous stem cells of lung may play a role in the effect of MSC-CM in endotoxin-induced ALI.