Fig. 5

The role of autophagy in inflammatory cytokine-induced apoptosis of MSCs. When MSCs were transplanted into the inflammatory microenvironment of CLP mice, inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), induced apoptosis of MSCs by activating caspase 3. Meanwhile, these inflammatory cytokines induced autophagy of MSCs. Autophagy also inhibited the expression of bcl-2 via suppression of the reactive oxygen species (ROS)/mitogen-activated protein kinase 1/3 (ERK) pathway, which promoted the activation of caspase 3 and led to apoptosis of MSCs. On the contrary, inhibition of autophagy in MSCs activated the ROS/ERK pathway, which reduced apoptosis of MSCs via upregulating Bcl-2 expression and inhibiting caspase 3 activation