Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response

Figure 1

The red arrow shows the classical pathway of LPS-mediated activation of TLR4 that further leads to pyroptosis and releases of IL-1β and IL-18. The green arrow shows the noncanonical pathway through which LPS directly activates caspase-4/5/11 without TLR4. The blue arrow shows the negative feedback of pyroptosis on autophagy wherein caspase-1-mediated activation of caspase-3 leads to enhanced autophagy and inactivation of GSDMD. The brown arrow shows RAPA-mediated deactivation of the inhibitory effect of mTOR on Atg7 that causes Atg7 to activate caspase-3. We surmise that RAPA is also more destructive to GSDMD and inhibits pyroptosis.