The Pharmacologically Active Alkaloid Cryptolepine Activates a Type 1 Interferon Response That Is Independent of MAVS and STING Pathways

Figure 8

Proposed upregulation of the IFN-1 response pathway by cryptolepine. Cytosolic RNA is detected by the MDA5 or RIG-1 which leads to the activation of IRF3 via the TBK1. However, cytosolic DNA is recognised by cGAS which then stimulates the STING-dependent signalling, leading to the phosphorylation of IRF3. The phosphorylated IRF3 homodimerises and moves into the nucleus causing the release of the IFN-1 (mainly IFN-α/β). The secreted IFNs simulate the later phase of the IFN-1 pathway (JAK-STAT axis) through the IFNARs, which transmit a cascade of signalling events to activate the promoters of ISGF3 and induce the production of numerous IFN-responsive proteins which facilitate anticancer and antiviral responses. This study has demonstrated that cryptolepine activates the IFN-1 response pathway via the JAK-STAT axis (as indicated by arrows) but is independent of the first phase of the pathway (as indicated by a crossed arrow). CRYPT: cryptolepine.