Mesenchymal Stem Cells Attenuate Cisplatin-Induced Nephrotoxicity in iNOS-Dependent Manner

Figure 6

MSC-derived NO is important for activation of IDO in TNF-α-stimulated MSCs. (a) Expression of IDO and iNOS in nonstimulated and TNF-α-stimulated MSCs. (b) Concentration of kynurenine in supernatants of nonstimulated MSCs, TNF-α-stimulated MSCs, and TNF-α-stimulated MSCs cultured in the presence of L-NMMA. . (c) Proposed mechanism of MSC-based immunomodulation of cisplatin-induced nephrotoxicity: After cisplatin-induced kidney injury, MSCs migrate in the kidneys as a response to the inflammatory cytokines and chemokines. Under inflammatory conditions, TNF-α provokes MSCs to express iNOS and to produce NO which, in turn, increases IDO activity and augment MSC-based immunomodulation resulting with attenuated number of inflammatory TNF-α-producing DCs and IFN-γ- and IL-17-producing T cells and increased number of immunosuppressive IL-10-producing DCs and regulatory T cells in injured kidneys.

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