Accumulating evidence suggests that mesenchymal stem cells (MSCs) may decrease destructive inflammation and reduce tissue loss. Tumor necrosis factor-α (TNF-α) plays a central role in induction of proinflammatory signaling and paradoxically activates intracellular anti-inflammatory survival pathways. In this study, we investigated whether TNF-α could induce a chemotactic effect on human MSCs and stimulate their production of anti-inflammatory factors in vitro, as well as determined mechanisms that mediated this effect. Migration assays demonstrated that TNF-α had a chemotactic effect on MSCs. TNF-α increased both hepatocyte growth factor (HGF) mRNA expression in MSCs and HGF secretion in conditioned medium. These effects were dependent on the p38 MAPK and PI3K/Akt, but not JNK and ERK signaling pathways. Furthermore, these effects were inhibited by a specific neutralizing antibody to TNF receptor II, but not TNF receptor I. We conclude that TNF-α can enhance human MSCs migration and stimulate their production of HGF. These effects are mediated via a specific TNF receptor and signaling pathways.
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