2022 Volume 47 Issue 1 Pages 19-33
The immunomodulatory ability of mesenchymal stem cells（ MSCs） is synergistically regulated through cell contact-dependent mechanisms and secretion of soluble factors. TGF-β1 plays an important role in immunosuppression. In this study, the expression of TGF-β1-induced inflammation-related cytokines, chemokines, and growth factors in the human MSC line, β1 stimulation. TGF-β1-induced expression of IL-6 was attenuated by a TGF-β receptor inhibitor and an MEK inhibitor. These results indicate that TGF-β1 increases IL-6 expression via the MEK pathway in human MSCs. Considering that TGF-β1 increased the expression levels of both NGF and IL-6 in the MSCs, we further investigated the effect of the cytokines secreted from UE7T-13 cells on neurite extension of neuronal PC12 cells. We found that the neurite extension in PC12 cells was significantly enhanced in the conditioned medium derived from TGF-β1-pretreated UE7T-13 cells. In addition, it was significantly enhanced by the indirect co-culture of PC12 cells and TGF-β1-stimulated UE7T13 cells under transwell conditions. Interestingly, these enhancements of neurite extension mediated using the conditioned medium or indirect co-culture were negated by the addition of a neutralizing antibody against the soluble IL-6 receptor in the culture media. We also confirmed that the administration of both IL-6 and soluble IL-6 receptors to PC12 cells did not promote these neurite extensions. Overall, these results suggest that NGF secreted from TGF-β1-stimulated MSCs induces neuronal differentiation of PC12 cells, which is further enhanced by IL-6 secreted from MSCs.
