Fig. 5

The relationship between autophagy and cytokines. Autophagy activation can promote or inhibit the secretion of cytokines to control tumor development. IL-1 can induce autophagy by SAPK/JNK signaling pathway, and autophagy represents a negative impact on IL-1 production by inhibiting the interaction between TLR4, TLR3, LPS and ROS accumulation, resulting in NF-κB signaling pathway inhibition. IL-2 boosts autophagy induction by promoting ATG5-beclin1-HMGB1 complex formation, however, autophay suppresses NF-κB-mediated IL-2 production. IL-6 exerts anti-autophagic effects by activating p-STAT3 and reducing the protein levels of LC3-II and Beclin 1, in addition, IL-6 promotes autophagy AMPK activation and mTORC1 inhibition, and Akt activation. Mutually, autophagy promotes the release of IL-6 by activating NF-κB pathway. IL-10 activates the JAK/STAT3 and PI3K/Akt/mTORC1 pathways, resulting in autophagy inhibition. IL-12 induces autophagy through suppressing the AKT/mTOR/STAT3 and PI3K/Akt pathways and activating AMPK pathway, and autophagy decreases IL-12 release by inhibiting inflammation. IL-23 contributes to autophagy inhibition and ROS accumulation by triggering AKT/mTOR/NF-κB pathway, and autophagy decreases the production of IL-23, TNFα and IFN by inhibiting IL-1β-mediated NF-κB signaling pathway. TNF represses autophagy by decreasing lysosomal acidification, and autophagy inhibits TNF-α expression through blocking p38MAPK phosphorylation and TRAF6 expression. IFNs induce autophagy by activating JAK/STAT and JAK1/2, PI3K and p38MAPK pathways, and suppress autophagy by decreasing autophagosome formation and the expression of autophagy-related genes ATG5 and GABARAP. TGF-β has been demonstrated to activate autophagy by Smads and JNK signal pathways, but autophagy decreases mature TGF-β protein levels as a result of increased degradation. In this figure, IL-10 and TGF-β enhance tumor development, other cytokines suppress tumor development