TNF-α enhances vascular cell adhesion molecule-1 expression in human bone marrow mesenchymal stem cells via the NF-κB, ERK and JNK signaling pathways

The migration of circulating mesenchymal stem cells ( MSCs) to injured tissue is an important step in tissue regeneration and requires adhesion to the microvascular endothelium. The current study investigated the underlying mechanism of MSC adhesion to endothelial cells during inflammation. In in vitro MSC culture, tumor necrosis factor-a (TNF-alpha) increased the level of vascular cell adhesion molecule-1 (VCAM-1) expression in a dose-dependent manner. The nuclear factor-kappa B (NF-kappa B), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathway inhibitors, pyrrolidine dithiocarbamate (PDTC), U0126 and SP600125, respectively, suppressed VCAM-1 expression induced by TNF-alpha at the mRNA and protein levels (P<0.05). TNF-alpha augmented the activation of NF-kappa B, ERK and JNK, and promoted MSC adhesion to human umbilical vein endothelial cells; however, the inhibitors of NF-kappa B, ERK and JNK did not affect this process in these cells. The results of the current study indicate that adhesion of circulating MSCs to the endothelium is regulated by TNF-alpha-induced VCAM-1 expression, which is potentially mediated by the NF-kappa B, ERK and JNK signaling pathways.