Background/aims: Human umbilical cord mesenchymal stem cells (hUC-MSCs) possess immunosuppressive activities but the mechanisms of such activities are not fully understood. Here, we investigated the role of IL-6, one of the characteristic factors of MSCs, in the immunoregulating effect of hUC-MSCs on CD4(+) T lymphocytes.
Methods: The condition media from human peripheral blood mononuclear cells (hPBMCs) or CD14+/- cell were tested if stimulating IL-6 production by hUC-MSCs. The related signaling pathway of IL-6, and the immunosuppressive activity of IL-6 on CD4(+) T lymphocytes were studied.
Result: IL-6 production was dramatically increased by hUC-MSCs when co-culturing with resting or activated hPBMCs. CD14(+) monocytes-paracrined IL-1β promoted the secretion of IL-6 by hUC-MSCs via JNK and NF-κB signaling pathway. Blocking of PGE2 synthesis did not affect the secretion of IL-6, anti-IL-6 antibody was not able to reverse hUC-MSCs-mediated inhibition on CD4(+) T lymphocytes. IL-6 did not mediate the suppressive activity of IL-1β-hUC-MSCs- PGE2 on CD4(+) T cell.
Conclusion: CD14(+) monocytes-paracrined IL-1β promotes IL-6 secretion by hUC-MSCs through activating JNK and NF-κB signaling pathway. However, increased IL-6 production does not contribute to immunosuppressive activity of IL-1β-hUC-MSCs- PGE2 on CD4(+) T cells.
Copyright © 2012 S. Karger AG, Basel.