Direct derivation of human induced pluripotent stem cells into neural precursor cells and differentiation of these into neurons holds great promise in the
cell therapy of
neurodegenerative diseases. However, the availability and survival rate of neurons requires improvement. In the present study, it was found that the addition of 5 ng/ml leukocyte inhibitory factor (LIF) during the process of differentiation significantly improved the expression of neuron‑specific class III β‑tubulin (TUJ1) and microtubule‑associated protein 2 (MAP2), as detected by immunofluorescence and western blotting. In addition, LIF improved the cell viability, increased the expression of phosphorylated‑protein kinase B (AKT), downregulated the expression of proinflammatory
cytokines, including interleukin‑1α (IL‑1α) and
tumor necrosis factor‑α (TNF-α), and upregulated the expression of anti‑inflammatory
cytokines, including interleukin‑10 (IL‑10) and transforming growth factor‑β (TGF-β). After adding the
phosphatidylinositol 3-kinase (PI3K)/AKT signaling inhibitor
LY294002 or
wortmannin to the LIF differentiation group, LIF-induced changes in the
protein expression of TUJ1 and MAP2 were reversed, but this effect could not be prevented by
rapamycin, a mechanistic target of
rapamycin signaling inhibitor. The expression of
cytokines associated with
inflammation and cell viability was reversed by
LY294002 and
wortmannin, but not by
rapamycin. In conclusion, LIF could improve neuronal differentiation and survival through the activation of PI3K/AKT signaling and the anti‑inflammatory effect. The anti‑inflammatory effect may be mediated by the activation of PI3K/AKT.